Publications by authors named "Yaser Mansoori"

29 Publications

  • Page 1 of 1

Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer.

J Transl Med 2021 08 26;19(1):364. Epub 2021 Aug 26.

Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Background: Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes.

Methods: A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC.

Results: According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein-protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis.

Conclusions: Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-021-03026-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390237PMC
August 2021

Perturbation of miR-146b and relevant inflammatory elements in esophageal carcinoma patients supports an immune downregulatory mechanism.

Pathol Res Pract 2021 Sep 20;225:153560. Epub 2021 Jul 20.

Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background: Esophageal Cancer is known as one of the deadliest cancers worldwide with the squamous cell carcinoma (ESCC) being the predominant subtype. There is a growing body of evidence linking the dysregulated microRNA (miRNA) pathway of immune cells to the progression of several tumors. In a previous study, we investigated molecular alterations pertaining to miR-146a and some components of NF-kB signaling pathway and proposed a possible immune downregulatory mechanism in peripheral blood mononuclear cells (PBMCs) of ESCC patients. Here, we further scrutinized other components of this pathway by evaluating PBMC levels of miR-146b, TLR4, IL10, and TNFA.

Methods: Gene expressions were quantified using RT-qPCR assays. To prevent the vulnerability of results to the expression instability of reference genes, nine additional transcripts were quantified, and stable reference genes for normalizing qPCR data were identified using the NormFinder and the geNorm algorithms. The efficiency-corrected normalized relative quantity values were used to compare gene expressions among study groups.

Results: The PBMC expression of miR-146b and TNFA was downregulated in ESCC patients as compared to healthy subjects. While the level of TLR4 was not different among the study groups, the PBMC level of IL10 was upregulated in ESCC patients. Logistic regression analyses coupled with the ROC curve and cross-validation analysis suggested that PBMC expression may serve as potential candidate biomarker for discriminating ESCC patients from healthy subjects.

Conclusion: The present findings, in line with our previous report, propose a particular gene expression pattern in PBMCs of ESCC patients, providing evidence in support of an immune downregulatory mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2021.153560DOI Listing
September 2021

Critical roles of microRNA-196 in normal physiology and non-malignant diseases: Diagnostic and therapeutic implications.

Exp Mol Pathol 2021 Jun 21;122:104664. Epub 2021 Jun 21.

Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

MicroRNAs (miRNAs) have emerged as a critical component of regulatory networks that modulate and fine-tune gene expression in a post-transcriptional manner. The microRNA-196 family is encoded by three loci in the human genome, namely hsa-mir-196a-1, hsa-mir-196a-2, and hsa-mir-196b. Increasing evidence supports the roles of different components of this miRNA family in regulating key cellular processes during differentiation and development, ranging from inflammation and differentiation of stem cells to limb development and remodeling and structure of adipose tissue. This review first discusses about the genomic context and regulation of this miRNA family and then take a bird's eye view on the updated list of its target genes and their biological processes to obtain insights about various functions played by members of the microRNA-196 family. We then describe evidence supporting the involvement of the human microRNA-196 family in regulating critical cellular processes both in physiological and non-malignant inflammatory conditions, highlighting recent seminal findings that carry implications for developing novel therapeutic or diagnostic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexmp.2021.104664DOI Listing
June 2021

Circular RNA hsa_circ_0044234 as distinct molecular signature of triple negative breast cancer: a potential regulator of GATA3.

Cancer Cell Int 2021 Jun 14;21(1):312. Epub 2021 Jun 14.

Medical Genetic Ward, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, Iran.

Background: Circular RNAs (circRNAs) have been implicated in the initiation and development of breast cancer as functional non-coding RNAs (ncRNA). The roles of circRNAs as the competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) have also been indicated. However, the functions of circRNAs in breast cancer have not been totally elucidated. This study aimed to explore the clinical implications and possible roles of circ_0044234 in carcinogenesis of the most problematic BC subtype, triple negative breast cancer (TNBC), which are in desperate need of biomarkers and targeted therapies.

Methods: The importance of circ_0044234 as one of the most dysregulated circRNAs in TNBC was discovered through microarray expression profile analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the downregulation of circ_0044234 in triple negative tumors and cell lines versus non-triple negative ones. The bioinformatics prediction revealed that circ_0044234 could act as an upstream sponge in the miR-135b/GATA3 axis, two of the most dysregulated transcripts in TNBC.

Results: Our experimental investigation of circ_0044234 expressions in various BC subtypes as well as cell lines reveals that TNBC expresses circ_0044234 at a substantially lower level than non-TNBC. The ROC curve analysis indicates that it could be applied as a discriminative biomarker to identify TNBC from other BC subtypes. Moreover, circ_0044234 expression could be an independent prognostic biomarker in BC. Interestingly, a substantial inverse expression correlation was detected between circ_0044234 and miR-135b-5p as well as between miR-135b-5p and GATA3 in breast tumors.

Conclusions: The possible clinical usefulness of circ_0044234 as a promising distinct biomarker and upcoming therapeutic target for TNBC have been indicated in this research. Our comprehensive approach revealed the potential circ_0044234/miR135b-5p/GATA3 ceRNA axis in TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-02015-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201848PMC
June 2021

A methylation signature at the CpG island promoter of estrogen receptor beta (ER-β) in breasts of women may be an early footmark of lack of breastfeeding and nulliparity.

Pathol Res Pract 2021 Feb 28;218:153328. Epub 2020 Dec 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Although little is known regarding the mechanisms behind the onset of breast cancer (BC) through reproductive risk factors, new researches have highlighted some early tumor-related methylation footmarks in the breast tissue of apparently clinically healthy women as their potential epigenetic mechanism. Previous evidence supports that the estrogen receptor beta (ER-β), whose anti-cancer roles had already been revealed in BC, is downregulated in the breasts of healthy nulliparous women. Nevertheless, data on such a link about its methylation alterations have not been reported. The goal of current study was to determine possible methylation alterations at CpG island promoter of the ER-β gene, including promoter 0 N and exon 0 N, in relation to aspects of reproductive history in the healthy breasts. The DNA was extracted from the breasts of 120 subjects undergoing cosmetic mammoplasty. Thereafter, the methylation levels of targeted regions in ER-β gene were determined by using MeDIP-qPCR assay. The results revealed that ER-β exon 0 N had no methylation in 84.2 % of the women, whereas the rest, comprising 2.5 % and 13.3 % of the samples, showed a lower and higher of its methylation, respectively. Interestingly, nulliparous women were found to have an elevated methylation level of the ER-β exon 0 N than parous women (P = 0.036). Moreover, we observed a high methylation of the ER-β exon 0 N in the breasts of non-breastfeeding women compared to breastfeeding subgroup (P = 0.048). Likewise, the non-breastfeeding subgroup showed exon 0N high methylation in comparison to women with breastfeeding >24 months (P = 0.023). Finally, although we found that 6.67 % of the samples had a high methylation level at the promoter 0N, no any relationship was found between its methylation and reproductive history. These results may provide key clues to revealing the epigenetic mechanism through which the nulliparity and lack of breastfeeding influencing the risk factor of BC as well as introducing the potential new early prediction and prevention strategies. Although further investigations need to be done in order to gain a better understanding the roles of these epigenetic signatures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153328DOI Listing
February 2021

Faculty retention in regional medical schools in Iran: a qualitative content analysis.

BMC Med Educ 2021 Jan 6;21(1):24. Epub 2021 Jan 6.

Medical Education Research Center, Fasa University of Medical Sciences, Fasa, Iran.

Background And Purpose: Recruitment and retention of competent faculty members are important in maintaining and improving the quality of education and research performance of universities. The aim of the present study was to find out the faculty members' views, experiences, and attitudes to identify the reasons for faculty attrition and retention in regional medical schools in Iran.

Methods: In this qualitative study, we used a content analysis method. The participants included 12 faculty members who had been transferred to type I universities, four faculty members who had applied for transfer, four with more than 10 years of experience and working in the type 3 universities with no intention to be transferred. Data were collected using semi-structured interviews, which were conducted either face-to-face or via phone calls. The interview was developed for this study (Supplementary file). To measure the trustworthiness of the data, we evaluated four components of credibility, transferability, dependability, and conformability, as proposed by Lincoln and Guba.

Results: The findings were classified into three categories and 14 subcategories. The first category was "retention facilitators" including four subcategories of facilitated communication, proximity to major universities, gaining experience, and support by authorities. The second category was "retention threats" including six subcategories of social infrastructure, individual dimension, occupation dimension, economic dimension, sense of respect, and executive management. The third category was "retention strategies" which included four subcategories of recruitment and promotion processes, inter-university collaboration with type I universities, facilitation of the scientific growth, and fulfilment of the safety needs.

Conclusion: Several factors play a role in the faculty members' retention in regional medical schools in Iran. Authorities can create a more positive environment by devising a suitable reward system, supporting academic activities, and increasing the level of faculty autonomy practically to develop a sense of belonging among them and reduce the intention to be transferred among their human resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12909-020-02473-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788721PMC
January 2021

Dysregulated Expression of miR-146a and Its Associated Immune Effectors in Peripheral Blood Mononuclear Cells of Esophageal Carcinoma Patients.

Immunol Invest 2020 Oct 2:1-11. Epub 2020 Oct 2.

Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Esophageal cancer is one of the least studied aggressive tumors, with the squamous cell carcinoma (ESCC) being the most frequent histological type around the world. Growing evidence has shown that the abnormal expression of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) is closely related to the pathogenesis of cancers. MiR-146a is a crucial regulator of inflammatory cascades. There is currently no data available regarding the possible role of miR-146a in PBMCs of ESCC patients. We evaluated the expression of miR-146a, as well as its target genes (IRAK1 and TRAF6) and its associated immune effectors (NF-κB1, IL1B, and IL6) in PBMCs of 40 ESCC patients and 50 control subjects. The geometric mean expression of five transcripts was used for normalizing expressions. The PBMC level of miR-146a, as measured by RT-qPCR, was upregulated, whereas levels of its target genes, IRAK1 and TRAF6, were downregulated in ESCC patients. NF-κB1 and IL6 was downregulated in PBMCs of ESCC patients. There was no difference in terms of the IL1B level between patients and the control group. Logistic regression and receiver operating characteristic curve analysis suggested that a model with PBMC levels of either NF-κB1+ IL6 or NF-κB1+ miR-146a as predictors may discriminate ESCC patients from subjects of the control group. Our findings, in the context of the current literature, may suggest a possible downregulatory mechanism of immune responses in PBMCs of ESCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2020.1828454DOI Listing
October 2020

Peripheral Blood Mononuclear Cells Expression Levels of miR-196a and miR-100 in Coronary Artery Disease Patients.

Immunol Invest 2020 Sep 15:1-11. Epub 2020 Sep 15.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

As a chronic inflammatory disease, coronary artery disease (CAD) is a common cause of death worldwide. Dysregulation of microRNA expression levels in peripheral blood mononuclear cells (PBMCs) may contribute to CAD and serve as a potential diagnostic biomarker. Here, we evaluated PBMC expression of two CAD-related inflammatory miRNAs, miR-196a and miR-100, in PBMCs of CAD patients with significant stenosis (CAD, n: 72), patients with insignificant coronary stenosis (ICAD, n: 30), and controls (n: 74) and checked whether they can segregate study groups. MiRNA expression was evaluated using the standard stem-loop RT-qPCR method. MiR-196a expression was downregulated in ICAD compared to CADs and healthy groups. MiR100 expression levels were not different between groups. The receiver operating characteristic (ROC) curve analysis acquainted that miR-196a expression levels in PBMC could segregate CAD individuals or any of its clinical manifestations (i.e. unstable angina, stable angina, acute myocardial infarction) from ICADs. In conclusion, this study reported a distinct miR-196a expression pattern in PBMCs of all patient groups and recommended a biomarker potential for miR-196a in discriminating ICADs from CADs or healthy controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2020.1791177DOI Listing
September 2020

Expression and clinicopathological significance of AOC4P, PRNCR1, and PCAT1 lncRNAs in breast cancer.

Pathol Res Pract 2020 Oct 21;216(10):153131. Epub 2020 Jul 21.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Long none coding RNAs (lncRNAs) AOC4P, PRNCR1, and PCAT-1 are dysregulated in various types of malignancies. However, their expression and clinicopathological significances are uncertain in breast cancer (BC). Quantitative real-time polymerase chain reaction (RT- qPCR) was used to measure the expression levels of the selected lncRNAs in tumor tissues obtained from 50 BC patients compared to the normal adjacent tissues (NATs) and 50 clinically healthy normal tissues. Our results revealed a significant downregulation of AOC4P, however, upregulated PRNCR1 and PCAT1 were found in tumor tissues compared to NATs and clinically healthy normal tissues (P < 0.05). Interestingly, remarkable decreased expression of AOC4P was observed in NATs than clinically healthy normal tissues. Dysregulation of the lncRNAs was correlated with worse outcomes of patients. Furthermore, our data showed that the altered expression levels of lncRNAs AOC4P, PRNCR1, and PCAT1 might be occurred through the function of demographic and reproductive variables. Taken together, the altered regulation of AOC4P, PRNCR1, and PCAT1 may highlight their crucial roles in BC development and pathogenesis. Our findings also proposed demographic and reproductive variables as risk factors in BC through the possible influence on the expression of the studied lncRNAs. Nevertheless, further explorations are required to elucidate the more detailed functions of these lncRNAs in BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153131DOI Listing
October 2020

Integrative analyses of triple negative dysregulated transcripts compared with non-triple negative tumors and their functional and molecular interactions.

J Cell Physiol 2019 12 12;234(12):22386-22399. Epub 2019 May 12.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Triple-negative (TN) tumors are a subtype of breast cancer with aggressive behaviors and limited targeted therapies. Microarray studies were not concerned with interactions and functional relations of dysregulated transcripts. Here, we aimed to conduct integrative strategy to analyze gene and miRNA available microarray data as well as bioinformatic analyses to catch a more inclusive picture of pivotal dysregulated transcripts and their interactions in TN tumors. Several online datasets and offline bioinformatic tools were used to detect differentially expressed (DE) transcripts, both protein and nonprotein coding, in TN compared with non-TN tumors and their functional and molecular interactions. Sixteen upregulated and 58 downregulated genes with a log fold change higher or equal to | 2 | were identified, including nine transcription factors. Coexpression network revealed EN1 as a hub gene, moreover Kaplan-Meier plotter survival analysis indicated that it was an appropriate prognostic marker for TN patients with breast cancer. Functional annotation analysis of protein-protein interaction network showed FOXM1 as an upexpressed and ESR1 as a downexpressed hub genes are suitable targets as far as antitumor protein therapy is concerned in TN breast cancers. The consensus analysis of two microRNA datasets revealed seven DE miRNAs. The gene-transcriptional factor (TF)-miRNA network revealed mir-135b and mir-29b are the hub nodes and involved in feedback loops with GATA3. This study suggests that dysregulated TFs and miRNAs have pivotal roles in regulation of TN oncotranscriptomic profile and might become both biomarkers and therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.28804DOI Listing
December 2019

The Effect of Mesenchymal Stem Cells on the Expression of IDO and Qa2 Molecules in Dendritic Cells.

Adv Pharm Bull 2019 Feb 2;9(1):56-63. Epub 2019 Feb 2.

Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Mesenchymal stem cells (MSCs) have been shown to reduce the activity of immune cells, including dendritic cells (DCs). But the exact mechanism of mesenchymal inhibition of DCs is still unknown. In this study, the effect of mesenchymal cells on the expression of indoleamine dioxygenase (IDO) and Qa2 molecules in DCs was evaluated. MSCs and DCs were respectively isolated from the bone marrow and spleen of BALB/c mice. Then DCs were co-cultured with MSCs in the present and absence of lipopolysaccharides (LPS). Then the expression of mRNA and protein of IDO and Qa2 molecules were investigated in DCs that were treated with MSCs. The expression of IDO and Qa2 mRNA in DCs that were treated with MSCs did not significantly differ from the control group. The expression of IDO protein in DCs that were cocultured with MSCs (in 1:10 and 1:50 ratios) in absence of LPS was increased, although they were not statistically significant (P values: 0.24 and 0.18, respectively). The expression of Qa2 protein in DCs that were co-cultured with MSCs (in 1:10 and 1:50 ratios) in presence of LPS was increased, although they were not statistically significant (P-values: 0.09 and 0.33, respectively). Our results denied the possibility that MSCs led to the induction of tolerogenic DCs by increasing the expression of the IDO and Qa2 immunomodulatory molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15171/apb.2019.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468229PMC
February 2019

Expression pattern of miR-21, miR-25 and PTEN in peripheral blood mononuclear cells of patients with significant or insignificant coronary stenosis.

Gene 2019 May 6;698:170-178. Epub 2019 Mar 6.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran. Electronic address:

Coronary artery disease (CAD) is primarily caused by atherosclerosis, which is a series of chronic inflammatory processes leading to the initiation and progression of vascular endothelial cell injury enhancing plaque formation. As critical components of the immune system, peripheral blood mononuclear cells (PBMCs) actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in altered PBMC expression pattern. This study explored PBMC expression levels of miR-21, miR-25 and PTEN in patients with angiographically proven significant coronary stenosis (the CAD group), patients with insignificant coronary stenosis (the ICAD group) and healthy subjects, and assessed potentials of PBMC expressions in discriminating groups of study subjects. In-silico analysis was also performed to obtain insights into CAD-related pathways and biological processes that may be influenced by altered miRNA expressions. A reduced level of PBMC miR-21 was observed in the ICAD group compared to the CAD group (P: 0.004) or healthy controls (P: 0.0001). PBMC miR-21 level was negatively correlated with the PTEN expression (Spearman r: -0.43, P: 3.9e-09). The PTEN expression was increased in the CAD or ICAD group compared to the control group (CAD vs. controls P: 0.0003, ICAD vs. controls P: 0.03). A stepwise increase in PBMC miR-25 levels was observed from healthy controls to ICADs and CAD patients (Kruskal-Wallis P: 7.68e-12). PBMC gene expressions had reasonable power to discriminate between pairs of study groups. PBMC miR-21 levels were able to discriminate ICADs from both CADs and controls and miR-25 levels had potentials to differentiate among all pairs of study groups (i.e. CADs-ICADs, CADs-controls, CADs-all other subjects, ICADs-controls). PBMC PTEN expression was able to discriminate patients with CAD or ICAD from control subjects. Overrepresentation enrichment analysis of experimentally validated targets of miR-21 and miR-25 highlighted key biological processes and pathways, such as "angiogenesis" and "leukocyte cell-cell adhesion", that may be influenced by dysregulation of PBMC miR-21 and miR-25. In conclusion, these findings suggest that patients with insignificant coronary stenosis may have a distinct PBMC miRNA expression profile than those with significant stenosis or healthy controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2019.02.074DOI Listing
May 2019

Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer?

J Cell Biochem 2019 08 28;120(8):12393-12401. Epub 2019 Feb 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform α is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR-α (progesterone receptor α) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR-α promoter CpG island was determined by using MeDIP-qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR-α promoter ( β = -0.790, SE = 0.362; P = 0.031). Although lactating women had more methylation than nonlactating women (P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28505DOI Listing
August 2019

The intricate role of miR-155 in carcinogenesis: potential implications for esophageal cancer research.

Biomark Med 2019 02 23;13(2):147-159. Epub 2019 Jan 23.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

MiRNAs have immerged as essential modulators of key cellular procuresses involved in post-transcriptional regulation of the human transcriptome. They are essential components of complex regulatory networks that modulate most important physiological functions of cells. MicroRNA-155 (miR-155) is a multifaceted regulator of cell proliferation, cell cycle, development, immunity and inflammation that plays pivotal, and sometimes contradictory, roles in numerous cancers including esophageal cancer. Here, we review the intricate role of miR-155 in cancer by exemplifying carcinogenesis of various tumors, focusing on recent findings that may provide a link between miR-155 and esophageal cancer-related pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm-2018-0127DOI Listing
February 2019

miRNA Polymorphisms and Risk of Cardio-Cerebrovascular Diseases: A Systematic Review and Meta-Analysis.

Int J Mol Sci 2019 Jan 12;20(2). Epub 2019 Jan 12.

Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz 5138663134, Iran.

Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range of conditions including cardiovascular diseases (CVDs, especially coronary artery disease (CAD)), congenital heart disease (CHD) and cerebrovascular diseases (CBVDs, especially the ischemic stroke (IS)). An increasing number of studies are evaluating the association between different miRNA polymorphisms and risk of CCDs, but results have been inconclusive. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and risk of CCDs. PubMed, Embase, Scopus, and Web of Science were queried to identify eligible articles. Odds ratios and 95% confidence intervals were used to assess the association of miRNA polymorphisms with CCD susceptibility. A total of 51 eligible articles evaluating the association of 31 miRNA polymorphisms were identified. Meta-analysis was performed for six miRNA polymorphisms. miR-146a rs2910164 (30 studies: 13,186 cases/14,497 controls), miR-149 rs2292832 (Nine studies: 4116 cases/3511 controls), miR-149 rs71428439 (Three studies: 1556 cases/1567 controls), miR-196a2 rs11614913 (20 studies: 10,144 cases/10,433 controls), miR-218 rs11134527 (Three studies: 2,322 cases/2,754 controls) were not associated with overall CCD. miR-499 rs3746444 was associated with CCD (20 studies: 9564 cases/8876 controls). In the subgroups, rs2910164 and rs3746444 were only associated with CVDs, especially CAD. In conclusion, the results support the existence of a role for miR-146a rs2910164 and miR-499 rs3746444 in determining susceptibility to CCDs, especially CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20020293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359604PMC
January 2019

Breast cancer-linked lncRNA u-Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding.

J Cell Biochem 2019 06 11;120(6):9869-9876. Epub 2018 Dec 11.

Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.

Recently, it has been revealed that estrogen-related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen-related long noncoding RNAs (lncRNAs) upstream Eleanor (u-Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer-free women who had undergone cosmetic mammoplasty. The expression levels of u-Eleanor and HOTAIR were measured using quantitative real-time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high-level expression of u-Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u-Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = -0.258; P = 0.036) and multivariate regression model (β = -0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u-Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28269DOI Listing
June 2019

Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer.

J Cell Physiol 2019 07 10;234(7):10080-10100. Epub 2018 Dec 10.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood. In the recent years, the newly discovered mechanism in the RNA world is "competing endogenous RNA (ceRNA)" which proposes regulatory dialogues between different RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). In the latest BC research, various studies have revealed that dysregulation of several ceRNA networks (ceRNETs) between these ncRNAs has fundamental roles in establishing the hallmarks of BC development. And it is thought that such a discovery could open a new window for a better understanding of the hidden aspects of breast tumors. Besides, it probably can provide new biomarkers and potential efficient therapeutic targets for BC. This review will discuss the existing body of knowledge regarding the key functions of ceRNETs and then highlights the emerging roles of some recently discovered ceRNETs in several hallmarks of BC. Moreover, we propose for the first time the "ceRnome" as a new term in the present article for RNA research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.27941DOI Listing
July 2019

Re: Genetic Polymorphism on Susceptibility to Nephrotoxic Properties of BTEXs Compounds.

J Occup Environ Med 2018 10;60(10):e560-e561

Research Center for Health Sciences, Institute of Health, Department of Occupational Health Engineering, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran Department of Occupational Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Department of Occupational Health Engineering, School of Public Health, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, Iran Non-Communicable Diseases Research Center, Department of Medical Genetics, Fasa University of Medical Sciences, Fasa, Iran Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Department of Epidemiology and Biostatistics, School of Public Health, Knowledge Utilization Research Center (KURC), Tehran University of Medical Sciences Tehran, Iran.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JOM.0000000000001406DOI Listing
October 2018

Effects of Genetic Polymorphism on Susceptibility to Nephrotoxic Properties of BTEXs Compounds.

J Occup Environ Med 2018 08;60(8):e377-e382

Research Center for Health Sciences, Institute of Health, Department of Occupational Health Engineering, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran (Dr Neghab); Department of Occupational Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran (Dr Nourozi); Department of Occupational Health Engineering, School of Public Health, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, Iran (Dr Shahtaheri); Non-communicable Diseases Research Center, Department of Medical Genetics, Fasa University of Medical Sciences, Fasa, Iran (Dr Mansoori); Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran (Dr Bazzaz); and Department of Epidemiology and Biostatistics, School of Public Health, Knowledge Utilization Research Center (KURC), Tehran University of Medical Sciences, Tehran, Iran (Dr Nedjat).

Objective: The aim of this study was to ascertain whether genetic polymorphism affects susceptibility of individuals to nephrotoxic potentials of benzene, toluene, ethyl-benzene, and xylenes (BTEXs).

Methods: Fifty BTEXs exposed workers with one or more abnormal parameter of kidney function and 232 referent subjects, with similar exposure history, free from any abnormal kidney parameters were investigated. Atmospheric concentrations of BTEXs were measured. In addition, genetic polymorphisms were determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP).

Results: The frequencies of GSTP1 Ile-Val/Val-Val, null GSTT1, and null GSTT1/GSTM1 genotypes and mean values of blood urea nitrogen and plasma creatinine were significantly higher, while average glomerular filtration rate was significantly lower in cases than in referent subjects.

Conclusion: These findings indicate that individuals carrying null GSTT1 or null GSTT1/GSTM1 are more susceptible to nephrotoxic properties of BTEXs compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JOM.0000000000001364DOI Listing
August 2018

Expression levels of breast cancer-related GAS5 and LSINCT5 lncRNAs in cancer-free breast tissue: Molecular associations with age at menarche and obesity.

Breast J 2018 11 21;24(6):876-882. Epub 2018 May 21.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Long noncoding RNAs (lncRNAs) constitute a major class of the human transcriptome which play crucial roles in the key biological processes of both normal and malignant breast cells. Although the aberrant expression of lncRNAs has been well-documented in breast cancer (BC), little is currently known about the association between their expression levels in the breast tissue of healthy women and BC risk factors, especially the reproductive or demographic characteristics that are among the most well-known BC risk modifiers. This study was an attempt to investigate the correlation between the expression levels of 2 breast cancer-related lncRNAs, including GAS5 and LSINCT5, and reproductive and demographic characteristics in 145 normal breast tissues that were obtained from women without breast cancer undergoing cosmetic surgery. Total RNA was extracted from fresh normal breast tissues, and the expression level of target lncRNAs was quantified using real-time qPCR. Differences in the mean normalized gene expression among the subgroups of different variables were analyzed. The expression levels of both genes was lower in the overweight-obese (BMI ≥ 25) subgroup than that in the normal BMI (BMI < 25) subgroup (GAS5 P = .019, LSINCT5 P = .036). Moreover, the expression level of GAS5 was negatively correlated with BMI (r: -.170, P: .041). The expression level of GAS5 was higher in women with late menarche (>13 years) than that with early menarche (≤13 years; P = .017). These findings may assist to obtain insights into the molecular mechanisms through which the reproductive or obesity-related estrogen changes contribute to the breast carcinogenesis. In conclusion, this study presents the first evidence for the presence of a link between the lncRNA expression and the reproductive or obesity related factors in the breast tissue of healthy women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbj.13067DOI Listing
November 2018

A link between expression level of long-non-coding RNA in breast tissue of healthy women and obesity.

Int J Biol Markers 2018 Nov 24;33(4):500-506. Epub 2018 Apr 24.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Epidemiological and experimental literature indicates that the risk of breast cancer incidence is strongly linked to hormone-dependent factors, including reproductive history and obesity. However, the molecular mechanisms underlying the association between these factors and breast cancer risk are poorly understood. The aim of this study, therefore, was to determine whether obesity and reproductive history are associated with expression levels of two breast cancer-related long non-coding RNAs (lncRNAs), namely and in cancer-free breast tissues of women.

Methods: In the current research, 145 healthy women were recruited, and the quantitative expression levels of the two lncRNAs were determined through qPCR assay after gathering the mammoplasty breast tissue samples.

Results: It was found that women with body mass index (BMI)≥30 kg/m and BMI 25-29 kg/m show a low expression of compared to the BMI<25 kg/m (=0.031 and =0.027, respectively). Then, the correlation analysis disclosed a negative correlation of low expression with increasing BMI (r=-0.194, =0.019). Interestingly, this analysis demonstrated a negative correlation between low expression of the and high BMI in women with menarche age below 14 (r=-221; =0.028). Lastly, it was also revealed that there was a negative association of the low expression level of with increasing BMI in women through regression models (B=-0.048, =0.019).

Conclusions: These findings suggest interesting clues about the links between high BMI and the expression levels of in non-diseased breasts that may help us better understand the underlying mechanisms through which obesity contributes to breast carcinogenesis. However, such results need more validations in future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1724600818762258DOI Listing
November 2018

Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity.

Arch Toxicol 2018 06 4;92(6):1983-1990. Epub 2017 Dec 4.

Department of Occupational Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR-RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-017-2104-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002464PMC
June 2018

Association of VDR gene polymorphisms with risk of relapsing-remitting multiple sclerosis in an Iranian Kurdish population.

Int J Neurosci 2018 Jun 16;128(6):505-511. Epub 2017 Nov 16.

a Noncommunicable Diseases Research Center , Fasa University of Medical Sciences , Fasa , Iran.

Purpose: The purpose of this study was to evaluate the association of VDR Apa-I, Bsm-I, Fok-I, Taq-I single nucleotide polymorphisms (SNPs) with multiple sclerosis (MS) risk in an Iranian Kurdish population.

Materials And Methods: A population including of 118 patients and 124 healthy matched controls were recruited to the study. Genotyping of the SNPs was accomplished using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: The frequency of allele T of Fok-I (P = 0.003) and allele C of Taq-I (P = 0.0003) was significantly different between case and control subjects and showed significant association with risk of MS (OR = 1.84, 95% CI = 1.23-2.76; OR = 1.98, 95% CI = 1.36-2.87, respectively). CT genotype (OR = 1.7, 95% CI = 1.05-2.99) of Fok-I and CC genotype (OR = 2.18, 95% CI = 1.05-4.52) of Taq-I showed a predisposing effect. Combined TT+TC vs. CC for Fok-I (OR = 2.15, 95% = CI 1.29-3.60) and combined CC+TC vs. TT for Taq-I (OR = 2.58, 95% CI 1.51-4.40) were susceptibility genotypes for MS. Apa-I and Bsm-I were not significantly associated with risk of MS (OR < 1, P > 0.05) and any genotypes in any genetic models were not significantly different between cases and controls (P > 0.05).

Conclusion: As a result, Fok-I and Taq-I showed significant association with risk of MS, while Apa-I and Bsm-I were not observed to be related to the risk of the disease in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00207454.2017.1398158DOI Listing
June 2018

Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?

Genet Test Mol Biomarkers 2017 Aug 14;21(8):464-470. Epub 2017 Jul 14.

1 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .

Background: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis.

Materials And Methods: Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay.

Results: The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m (p < 0.001) and BMI 25-29 kg/m (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m subgroup compared to the BMI 25-29 kg/m subgroup (p = 0.023).

Conclusion: These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2017.0028DOI Listing
August 2017

The SDF1 A/G Gene Variant: A Susceptibility Variant for Myocardial Infarction.

Genet Test Mol Biomarkers 2017 Aug 26;21(8):506-511. Epub 2017 Jun 26.

2 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .

Background: Although environmental factors play an important role in susceptibility to myocardial infarction (MI), genetic determinants also provide a significant contribution. This study aimed to determine whether or not MI susceptibility is influenced by the SDF1-rs1801157A/G and HHEX-rs1111875 A/G polymorphisms in an Iranian population.

Methods: A total of 120 patients with MI and 120 healthy controls were enrolled. Blood samples were collected from all the participants for genomic DNA extraction and testing. Polymorphism genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism technique.

Results: Multiple logistic regression analysis revealed that the A allele and AA genotype of the SDF1-rs1111875 polymorphism produce a significant risk of MI both before (crude odds ratio [OR] = 8.83, 95% confidence interval [95% CI] = 1.05-73.76, p = 0.025) and after adjustment (adjusted OR = 8.12, 95% CI = 5.02-19.42, p = 0.04). In contrast, the GG genotype of the SDF1-rs1111875 polymorphism provides a protective effect on MI in a recessive model (GG vs. AA+AG) before (crude OR = 0.57, 95% CI = 0.34-0.97, p = 0.037) and after adjustment (adjusted OR = 0.53, 95% CI = 0.3-0.82, p = 0.021). No association was found between the HHEX-rs1111875 A/G polymorphism alleles and the susceptibility to MI.

Conclusion: Taken together, the current findings suggest that the SDF1-rs1801157A/G gene variant may play an important role in relation to MI in this Iranian population. Nevertheless, more replication studies and meta-analyses should be carried out in this area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2017.0023DOI Listing
August 2017

miRNA-Related Polymorphisms in miR-423 (rs6505162) and PEX6 (rs1129186) and Risk of Esophageal Squamous Cell Carcinoma in an Iranian Cohort.

Genet Test Mol Biomarkers 2017 Jun 21;21(6):382-390. Epub 2017 Apr 21.

1 Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .

Aims: Iran is located in the Asian esophageal cancer belt. It is a high-risk region for esophageal squamous cell carcinoma (ESCC). The extent to which genetic components, especially variants within miRNAs or their binding sites, contribute to risk of ESCC in the region is not yet fully understood. Herein, tests were done on an Iranian cohort to evaluate the association of miRNA-related polymorphisms in miR-423 (rs6505162) and peroxisomal biogenesis factor 6 (PEX6) (rs1129186 within a miR-149-5p-binding site) with the risk of ESCC risk.

Methods: This study recruited 200 ESCC patients and 300 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Target genes and biological processes that are regulated by miR-423 and may be affected by a change in miR-423 expression were identified by in silico analysis.

Results: Logistic regression analyses revealed an association between rs6505162 and ESCC, assuming codominant (AA vs. CC, odds ratios, OR [95% confidence interval, CI]: 0.32 [0.15-0.69], p-value: 0.0076), recessive (AA vs. CC+CA, OR [95% CI]: 0.35 [0.16-0.73], p-value: 0.0027), and log-additive models (OR [95% CI]: 0.69 [0.52-0.91], p-value: 0.0084). No significant association was observed for PEX6 rs1129186. In silico analyses revealed several genes and biological processes that are regulated by miR-423 in ESCC.

Conclusion: This study identified the first evidence of an association of a miRNA-related variant with risk of ESCC in an Iranian cohort. PEX6 rs1129186 may not modulate the risk of ESCC in the cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2016.0346DOI Listing
June 2017

Influences of IL-1b-3953 C>T and MMP-9-1562C >T Gene Variants on Myocardial Infarction Susceptibility in a Subset of the Iranian Population.

Genet Test Mol Biomarkers 2017 Jan 8;21(1):33-38. Epub 2016 Nov 8.

2 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences , Fasa, Iran .

Aims: IL-1b-3953 C>T and MMP-9-1562C>T variants have been shown to be linked to the development of myocardial infarction (MI), although previous studies have reported inconsistent results. The aim of the present study was to determine whether these genetic variations are associated with MI susceptibility in an Iranian population.

Methods: In the current study, 117 patients with MI and 120 control group members were selected as participants. Peripheral blood samples were taken from all the subjects for genomic DNA extraction. Single nucleotide polymorphism (SNP) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays.

Results: Multiple logistic regression analysis revealed that the TT genotype of the IL-1b-3953 C>T polymorphism is associated with a significant MI protective effect in: the homozygote model after adjustment for MI risk factors (odds ratio [OR]: 0.18, confidence interval [95% CI] = 0.04-0.72; p = 0.01); and also in the recessive genetic model both before (OR: 0.39, 95% CI: 0.15-0.96, p = 0.04) and after (OR: 0.15, 95% CI: 0.04-0.58, p = 0.006) adjustment for MI risk factors. Furthermore, multiple logistic regression analysis indicated that the individuals with the TT genotype of the MMP-9-1562C>T polymorphism were significantly protected against MI in comparison with the CC genotype (OR: 0.01, 95% CI: 0.002-0.68, p = 0.03).

Conclusion: The findings suggest that the minor alleles of the two polymorphisms under study both have protective effects with respect to MI susceptibility in the Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2016.0240DOI Listing
January 2017

Significance of a common variant in the CDKAL1 gene with susceptibility to type 2 diabetes mellitus in Iranian population.

Adv Biomed Res 2015 11;4:45. Epub 2015 Feb 11.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Type 2 diabetes mellitus (T2DM) is a worldwide problem that threatens the public health and economies of all countries. A multifactorial etiology and interaction between environmental factors and genetic components are responsible for triggering and progression of T2DM. Recently, rs7754840 single nucleotide polymorphism (SNP) in the CDKAL1 gene was reported to be associated with T2DM in various populations. However, due to inconsistent results in various populations about the association of rs7754840 with T2DM, and lack of information in the Iranian population, we have evaluated its association with T2DM in a subset of the Iranian population from Isfahan province, central part of Iran.

Materials And Methods: The study included 140 patients and 140 controls selected based on the World Health Organization guidelines. Genomic DNA was extracted from blood samples and the rs7754840 SNP was genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay with specific primers and restriction enzyme (Ac1I).

Results: The frequency of the C allele in the cases was higher than that in the controls (72.9% vs. 65%; P = 0.045). Using logistic regression analysis, we found a significant risk association of CC genotype with T2DM susceptibility (OR = 2.319, 95% CI = 1.436-3.744, P = 0.001). Furthermore, compared with the CC genotype, individuals with the GC genotype had a lower risk (protective association) of developing T2DM (OR = 0.332, 95% CI = 0.202-0.547, P < 0.001).

Conclusions: We confirmed that there is a significant risk association between rs7754840 polymorphism and development of T2DM in a subset of the Iranian population from Isfahan province.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2277-9175.151256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358034PMC
March 2015

Association of interleukin-18 gene variants with susceptibility to visceral leishmaniasis in Iranian population.

Mol Biol Rep 2013 Jun 27;40(6):4009-14. Epub 2012 Dec 27.

Department of Immunology, Fasa University of Medical Sciences, Fasa, Fars, Iran.

Host resistance to Leishmania infection is mediated by cellular immune responses leading to macrophage activation and parasite killing. Interleukin-18 (IL-18) known as interferon-γ (IFN-γ) inducing factor, stimulates IFN-γ production by T cells. Taking into account the important role of IL-18 in the defense against visceral leishmaniasis (VL) and the known effect of IL-18 gene polymorphisms on its production, the aim of this study was to investigate the probable relationship between IL-18 gene polymorphisms and the susceptibility to VL. The study groups included 118 pediatric patients who suffered from VL and 156 non-relative healthy people as the controls from the same endemic area. IL-18 gene polymorphisms at the positions -656 G/T, -137 G/C and +105A/C (codon 35/3) were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). The results showed that the frequency of T allele at the position -656 was significantly higher in the controls, compared with that in the patients (P = 0.047), but it couldn't tolerate Bonferroni correction. Regarding the IL-18 genotypes, there was no significant difference between the patients and controls. Although the frequencies of ATG single haplotype and AGG/ATG double haplotype were significantly higher in the controls (P = 0.043) and the patients (P = 0.044), respectively, the two P values couldn't tolerate Bonferroni correction. Furthermore, a strong linkage disequilibrium was observed among the -656, -137 and +105 single nucleotide polymorphisms of IL-18 gene (all Ps < 0.001). In conclusion, this study suggests that the inheritance of T allele at the position -656 may be considered as a genetic factor for resistance to VL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-012-2479-xDOI Listing
June 2013
-->