Publications by authors named "Soudeh Ghafouri-Fard"

530 Publications

Evaluation of potential of miR-8073 and miR-642 as diagnostic markers in pancreatic cancer.

Mol Biol Rep 2022 May 20. Epub 2022 May 20.

Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Pancreatic cancer is a cancer with an insidious course. Since disease is often diagnosed at advanced stages, clinical outcome is impaired. Thus identification of biomarkers for this malignancy has importance in enhancement of patients' survival.

Methods And Results: In the current study, we assessed expression levels of miR-8073 and miR-642 in the circulation of 50 patients with pancreatic cancer and 50 controls. Plasma levels of miR-8073 and miR-642 were significantly higher in patients with pancreatic cancer compared with controls (P value < 0.0001 and P value = 0.0068, respectively). Plasma levels of miR-642 were inversely correlated with albumin levels (R=-0.28, P value = 0.049), WBC count (R=-0.35, P value = 0.01), as well as CRP level (R=-0.30, P value = 0.035). On the other hand, levels of this miRNA were positively correlated with lipase level (R = 0.29, P value = 0.042). Levels of miR-8073 were not correlated with any of the available parameters. Plasma levels of miR-8073 could separate patients with pancreatic cancer from controls with AUC, sensitivity and specificity values of 0.82, 0.77 and 0.78, respectively. miR-642 could differentiate these two groups with AUC, sensitivity and specificity values of 0.63, 0.58 and 0.78, respectively. Combination of these two parameters resulted in AUC, sensitivity and specificity values of 0.79, 0.77 and 0.78, respectively.

Conclusions: Taken together, these two miRNAs are suggested as possible blood markers for pancreatic cancer.
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http://dx.doi.org/10.1007/s11033-022-07476-0DOI Listing
May 2022

A review on the role of DANCR in the carcinogenesis.

Cancer Cell Int 2022 May 19;22(1):194. Epub 2022 May 19.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

DANCR is an RNA gene located on chr4. This gene has several splice variants. Up-regulation of DANCR has been reported in many types of cancers. This lncRNA is mainly located in the cytoplasm and regulates genes expression at post-transcriptional level. In fact, it acts as a molecular sponge for a variety of miRNAs, including miR-874-3P, miR-335, miR-149, miR-4319, miR-758-3p, miR-216a-5p, miR-874-3p, miR-33a-5p, miR-335-5p, miR-145-3p, miR-665, miR-345-5p and miR-125b-5p. DANCR also regulates activity of PI3K/AKT/NF-κB, Wnt/β-catenin, ERK/SMAD, MAPK, IL-6/JAK1/STAT3, Smad2/3, p53, FAK/PI3K/AKT/GSK3β/Snail pathways. In the current narrative review article, we summarize the roles of DANCR in the carcinogenesis, with an especial emphasis on its role in the development of osteosarcoma and lung, liver, pancreatic and colorectal cancers.
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http://dx.doi.org/10.1186/s12935-022-02612-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118872PMC
May 2022

A Comprehensive Review on Function of miR-15b-5p in Malignant and Non-Malignant Disorders.

Front Oncol 2022 2;12:870996. Epub 2022 May 2.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

miR-15b-5p is encoded by gene. This gene is located on cytogenetic band 3q25.33. This miRNA participates in the pathogenesis of several cancers as well as non-malignant conditions, such as abdominal aortic aneurysm, Alzheimer's and Parkinson's diseases, cerebral ischemia reperfusion injury, coronary artery disease, dexamethasone induced steatosis, diabetic complications and doxorubicin-induced cardiotoxicity. In malignant conditions, both oncogenic and tumor suppressor impacts have been described for miR-15b-5p. Dysregulation of miR-15b-5p in clinical samples has been associated with poor outcome in different kinds of cancers. In this review, we discuss the role of miR-15b-5p in malignant and non-malignant conditions.
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http://dx.doi.org/10.3389/fonc.2022.870996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108330PMC
May 2022

Interaction Between Non-Coding RNAs and Interferons: With an Especial Focus on Type I Interferons.

Front Immunol 2022 27;13:877243. Epub 2022 Apr 27.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Interferons (IFNs) are a group of cellular proteins with critical roles in the regulation of immune responses in the course of microbial infections. Moreover, expressions of IFNs are dysregulated in autoimmune disorders. IFNs are also a part of immune responses in malignant conditions. The expression of these proteins and activities of related signaling can be influenced by a number of non-coding RNAs. IFN regulatory factors (IRFs) are the most investigated molecules in the field of effects of non-coding RNAs on IFN signaling. These interactions have been best assessed in the context of cancer, revealing the importance of immune function in the pathoetiology of cancer. In addition, IFN-related non-coding RNAs may contribute to the pathogenesis of neuropsychiatric conditions, systemic sclerosis, Newcastle disease, Sjögren's syndrome, traumatic brain injury, lupus nephritis, systemic lupus erythematosus, diabetes mellitus, and myocardial ischemia/reperfusion injury. In the current review, we describe the role of microRNAs and long non-coding RNAs in the regulation of IFN signaling.
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http://dx.doi.org/10.3389/fimmu.2022.877243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091820PMC
May 2022

The interaction between human papilloma viruses related cancers and non-coding RNAs.

Pathol Res Pract 2022 May 7;234:153939. Epub 2022 May 7.

Department of Pathology, Shohada-e-Tajrish Educational Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Human papillomaviruses (HPVs) constitute a number of double-stranded DNA viruses with propensity to cause infection in squamous epithelial cells. Certain types of these viruses have been found to cause human cancers through delivering their oncoproteins E6 and E7. Since not all of infected patients develop malignant lesions, other factors might affect HPV-associate carcinogenic processes. A number of investigations have shown interaction between HPV-encoded proteins and a number of non-coding RNAs, principally microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Such interactions have been found to influence pathogenesis of HPV-related cancers. miR-21, miR-9, miR-143, miR-214 and let-7 are among miRNAs that contribute in the pathogenesis of HPV-related lesions. HOTAIR, SNHG8, SOX2OT, SNHG12, GABPB1-AS1, SOX21-AS1, DINO, HOST2, CCDST, FAM83H-AS1, TMPOP2 and CCEPR are examples of lncRNAs that contribute in this process. In the current review, we provide an outline of investigations that reported the impact of these transcripts in HPV-related cancers.
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http://dx.doi.org/10.1016/j.prp.2022.153939DOI Listing
May 2022

Downregulation of long non-coding RNAs in patients with bipolar disorder.

Sci Rep 2022 May 6;12(1):7479. Epub 2022 May 6.

Department of Cell and Molecular Biology, Faculty of Life Sciences and Technology, Shahid Beheshti University, Tehran, Iran.

The abnormal function of signaling cascades is currently a candidate in the pathophysiology of bipolar disorder (BD). One of the factors involved in activating these signals is oxidative stress. Some long non-coding RNAs (lncRNA) are involved in the oxidative stress. In this study, we compared expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the peripheral blood mononuclear cells (PBMC) from BD patients (n = 50) and healthy individuals (n = 50). Expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT were significantly reduced in patients with BD compared to controls. In sex-based analyses, down-regulation of these lncRNAs was revealed only in male BD patients compared to male healthy subjects. Also, in BD patients, all three lncRNAs showed a significant pairwise positive correlation in expression level. The area under curve values for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT was 0.66, 0.75, and 0.66, respectively. Thus, the ROC curve analysis showed that lncRNA-ROR might serve as a diagnostic biomarker for distinguishing between BD patients and controls. Altogether, the current study proposes a role for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these lncRNAs might be useful as potential biomarkers for BD.
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http://dx.doi.org/10.1038/s41598-022-11674-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076844PMC
May 2022

Incorporation of second-tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program.

J Clin Lab Anal 2022 May 2:e24471. Epub 2022 May 2.

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

Background: Nowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non-invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC-MS/MS) for the evaluation of the baby's risk of certain metabolic disorders.

Methods: This retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second-tier tests and secondary biomarkers to improve positive predictive value (PPV).

Results: Statistical data were recorded via call interviewing in 6-8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false-positive rate was 0.15%.

Conclusion: This study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second-tier tests and secondary biomarkers improves PPV of neonatal screening programs.
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http://dx.doi.org/10.1002/jcla.24471DOI Listing
May 2022

Interplay between PI3K/AKT pathway and heart disorders.

Mol Biol Rep 2022 May 2. Epub 2022 May 2.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as HO, Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury.
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http://dx.doi.org/10.1007/s11033-022-07468-0DOI Listing
May 2022

Interaction between non-coding RNAs, mRNAs and G-quadruplexes.

Cancer Cell Int 2022 Apr 29;22(1):171. Epub 2022 Apr 29.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

G-quadruplexes are secondary helical configurations established between guanine-rich nucleic acids. The structure is seen in the promoter regions of numerous genes under certain situations. Predicted G-quadruplex-forming sequences are distributed across the genome in a non-random way. These structures are formed in telomeric regions of the human genome and oncogenic promoter G-rich regions. Identification of mechanisms of regulation of stability of G-quadruplexes has practical significance for understanding the molecular basis of genetic diseases such as cancer. A number of non-coding RNAs such as H19, XIST, FLJ39051 (GSEC), BC200 (BCYRN1), TERRA, pre-miRNA-1229, pre-miRNA-149 and miR-1587 have been found to contain G-quadraplex-forming regions or affect configuration of these structures in target genes. In the current review, we outline the recent research on the interaction between G-quadruplexes and non-coding RNAs, other RNA transcripts and DNA molecules.
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http://dx.doi.org/10.1186/s12935-022-02601-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052686PMC
April 2022

Emerging role of circular RNAs in the pathogenesis of ovarian cancer.

Cancer Cell Int 2022 Apr 29;22(1):172. Epub 2022 Apr 29.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Ovarian cancer is a female malignancy with high fatality-to-case ratio, which is due to late detection of cancer. Understanding the molecular mechanisms participating in these processes would facilitate design of therapeutic modalities and identification of novel tumor markers. Recent investigations have shown contribution of circular RNAs (circRNAs) in the evolution of ovarian cancer. These transcripts are produced through a back-splicing mechanism. The enclosed configuration of circRNAs protects them from degradation and potentiates them as biomarkers. Several circRNAs such as circMUC16, circRNA_MYLK, circRNA-UBAP2, circWHSC1, hsa_circ_0013958, circFGFR3, hsa_circRNA_102958 and circ_0072995 have been found to be up-regulated in this cancer, acting as oncogenes. On the other hand, circ-ITCH, circPLEKHM3, circ_100395, circ_0078607, circATRNL1, circHIPK3, circRHOBTB3, circEXOC6B, circ9119 and CDR1as are among down-regulated circRNAs in ovarian cancer. Expression levels of circCELSR1, circ_CELSR1, circATL2, circNRIP1, circTNPO3 and hsa_circ_0000714 have been shown to affect resistance of ovarian cancer cells to chemotherapy. Moreover, circ_100395, circFGFR3, circ_0000554, circCELSR1, circ-PTK2, circLNPEP, circ-CSPP1, circ_0000745, circ_100395 and circPLEKHM3 have been shown to regulate epithelial-mesenchymal transition and metastatic ability of ovarian cancer cells. In the current review, we explain the roles of circRNAs in the evolution and progression of ovarian cancer.
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http://dx.doi.org/10.1186/s12935-022-02602-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052556PMC
April 2022

Synaptic plasticity and depression: the role of miRNAs dysregulation.

Mol Biol Rep 2022 Apr 20. Epub 2022 Apr 20.

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

Background: MicroRNAs (miRNAs) have been recently shown to exert several functional roles in the development and function of neurons. Moreover, numerous miRNAs are present in high abundance in presynaptic and postsynaptic sites regulating synaptic plasticity and activity through different mechanisms.

Methods: We searched PubMed and Google Scholar databases with key words "Synaptic plasticity", "miRNA" and "major depressive disorder.

Results: Synaptic plasticity has an essential role in the ability of the brain to integrate transitory experiences into constant memory traces. Thus, it participates in the development of neuropsychiatric diseases such as major depressive disorder (MDD). Most notably, MDD-related alterations in synaptic function have been found to be closely related with abnormal expression of miRNAs.

Conclusions: Several miRNAs such as miR-9-5p, miR-204-5p, miR-128-3, miR-26a-3p, miR-218, miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p, miR-323a-3p, miR-425-5p, miR-34a, miR-137, miR-204-5p, miR-99a, miR-134, miR-124-3p and miR-3130-5p have been shown to be involved in the regulation of synaptic plasticity in the context of MDD. In the current review, we elaborate the role of miRNAs in regulation of this important neuronal feature in MDD.
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http://dx.doi.org/10.1007/s11033-022-07461-7DOI Listing
April 2022

Expression analysis of vitamin D receptor and its related long non-coding RNAs in peripheral blood of patients with Parkinson's disease.

Mol Biol Rep 2022 Apr 15. Epub 2022 Apr 15.

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

Background: Parkinson's disease (PD) is a neurological condition that is associated with abnormal expression of several transcripts. Vitamin D receptor (VDR) is a possible participant in the pathogenesis of PD.

Methods And Results: In the present research project, we evaluated expressions of VDR and three functionally associated long non-coding RNAs with this signaling, namely SNHG6, SNHG16 and LINC00346 in PD patients versus normal controls. Level of SNHG6 transcripts was lower in total patients in comparison with total controls (Expression ratio (95% CI) 0.44 (0.17-1.08)) and in male patients compared with male controls (Expression ratio (95% CI) 0.29 (0.13-0.65)). On the other hand, expression of VDR was higher in total patients compared with total controls (Expression ratio (95% CI) 10.86 (4.37-26.72)) and in male patients compared with male controls (Expression ratio (95% CI) 22.16 (6.23-78.8)). There was no significant difference in expression of SNHG16 and LINC00346 between PD patients and controls. Amounts of SNHG6 and VDR transcripts could differentiate total PD patients from total controls with AUC values of 0.66 and 0.86, respectively.

Conclusions: Cumulatively, the results of the present investigation imply dysregulation of VDR signaling in PD and necessitate conduction of further functional studies.
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http://dx.doi.org/10.1007/s11033-022-07372-7DOI Listing
April 2022

Therapeutic Potential of Microvesicles in Cell Therapy and Regenerative Medicine of Ocular Diseases With an Especial Focus on Mesenchymal Stem Cells-Derived Microvesicles.

Front Genet 2022 29;13:847679. Epub 2022 Mar 29.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

These days, mesenchymal stem cells (MSCs), because of immunomodulatory and pro-angiogenic abilities, are known as inevitable factors in regenerative medicine and cell therapy in different diseases such as ocular disorder. Moreover, researchers have indicated that exosome possess an essential potential in the therapeutic application of ocular disease. MSC-derived exosome (MSC-DE) have been identified as efficient as MSCs for treatment of eye injuries due to their small size and rapid diffusion all over the eye. MSC-DEs easily transfer their ingredients such as miRNAs, proteins, and cytokines to the inner layer in the eye and increase the reconstruction of the injured area. Furthermore, MSC-DEs deliver their immunomodulatory cargos in inflamed sites and inhibit immune cell migration, resulting in improvement of autoimmune uveitis. Interestingly, therapeutic effects were shown only in animal models that received MSC-DE. In this review, we summarized the therapeutic potential of MSCs and MSC-DE in cell therapy and regenerative medicine of ocular diseases.
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http://dx.doi.org/10.3389/fgene.2022.847679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001951PMC
March 2022

Significant reduction of long non-coding RNAs expression in bipolar disorder.

BMC Psychiatry 2022 Apr 12;22(1):256. Epub 2022 Apr 12.

Department of Cell and Molecular Biology, Faculty of Life Sciences and Technology, Shahid Beheshti University, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have been recently emerged as critical modulators of oxidative stress pathway. Likewise, rising evidence currently highlights dysfunction of oxidative stress pathways in bipolar disorder (BD) patients.In the current study, we evaluated the expression levels of H19, SCAL1 (LUCAT1), RMST, MEG3 and MT1DP lncRNAs in the PBMC from 50 patients with BD and 50 control subjects (male/female ratio in each group: 70%/30%). Expression levels of SCAL1, RMST and MEG3 but not H19 and MT1DP were considerably decreased in BD patients compared with healthy individuals. Such significant decrease in the expression of MEG3, RMST and SCAL1 was only reported in male BD patients compared with male controls. Substantial pairwise correlations were observed between expression levels of these lncRNAs in BD subjects. The area under curve values for RMST, MEG3 and SCAL1 were 0.70, 0.63 and 0.61 respectively. On the basis of this finding, RMST had the best efficiency in the discrimination of disease status between BD patients and controls. Taken together, the current results suggest a role for MEG3, RMST and SCAL1 lncRNAs in the pathogenesis of BD. In addition, peripheral expression levels of these lncRNAs might serve as potential peripheral markers for BD.
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http://dx.doi.org/10.1186/s12888-022-03899-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004165PMC
April 2022

Interplay Between Non-Coding RNAs and Programmed Cell Death Proteins.

Front Oncol 2022 23;12:808475. Epub 2022 Mar 23.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti Universality of Medical Sciences, Tehran, Iran.

Programmed cell death (PDCD) family of proteins includes at least 12 members, function of seven of them being more investigated. These members are PDCD1, PDCD2, PDCD4, PDCD5, PDCD6, PDCD7 and PDCD10. Consistent with the important roles of these proteins in the regulation of apoptosis, dysregulation of PDCDs is associated with diverse disorders ranging from intervertebral disc degeneration, amyotrophic lateral sclerosis, immune thrombocytopenia, type 1 diabetes, congenital hypothyroidism, Alzheimer's disease to different types of cancers. More recently, the interaction between non-coding RNAs and different members of PDCD family is being discovered. In the current study, we described the functional interactions between PDCDs and two classes of non-coding RNAs, namely microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miR-21 and miR-183 are two miRNAs whose interactions with PDCDs have been assessed in different contexts. The lncRNAs interaction with PDCDs is mainly assessed in the context of neoplasia indicating the role of MALAT1, MEG3, SNHG14 and LINC00473 in this process.
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http://dx.doi.org/10.3389/fonc.2022.808475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983884PMC
March 2022

Intracranial Rosai Dorfman Disease Presented With Multiple Huge Intraventricular Masses: A Case Report.

Front Surg 2022 21;9:766840. Epub 2022 Mar 21.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Rosai-Dorfman disease (RDD) usually presents with painless cervical lymphadenopathy during the two first decades of life, with or without extranodal involvement. Exclusive extranodal manifestation, and especially central nervous system (CNS) involvement, is uncommon. The etiology remains unknown and definitive diagnosis is based on characteristic histopathological and immunohistochemical features showing S100(+) CD1a(-) RDD type histiocytes with emperipolesis. Most CNS cases are dural-based masses.

Case Presentation: Herein, we present a case of RDD in an 8-year-old boy, who presented with multiple huge intraventricular masses.

Conclusion: Regarding rare CNS involvement and lack of established evidence-based therapeutic approaches, reports of any individual case can supply further beneficial data concerning treatment approaches and long-term effectiveness of therapeutic strategies.
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http://dx.doi.org/10.3389/fsurg.2022.766840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977648PMC
March 2022

HLA alleles and haplotype frequencies in Iranian population.

Hum Antibodies 2022 ;30(2):79-96

Cell Therapy and Hematopoietic Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: HLA genotyping is a prerequisite for selection of suitable donors in the process of bone marrow transplantation.

Methods: In the current study, the frequencies of HLA-A, -B, -C and -DRB1 alleles and A-B-C-DRB1 haplotypes were assessed in 855 healthy Iranian persons using a low-resolution sequence specific primer (SSP) kit.

Results: Frequencies were compared between 11 subpopulations including Armani, Balouch, Bandari, Turk, Turkaman, Arab, Fars, Kurd, Gilaki, Lor and Mazani. In total, 17 HLA-A alleles were detected, one of which (HLA-A*74) was present only among Lors. HLA-A*23 and -A*26 were the most frequent HLA-A alleles among Armanis. HLA-A*23 was also common among Turkamans. HLA-A*11 and -A*26 were most frequent among the Balouch subpopulation. The former allele was also frequent among Bandaris. HLA-A*02 was identified as the most common HLA-A allele among Turk, Arab and Fars subpopulations. HLA-A*30 were strongly enriched among Gilakis. A total of 31 HLA-B alleles were detected across the target population. While all alleles were present among Fars subgroup, Armanis and Turkamans had the lowest degree of diversity among the alleles examined. Moreover, HLA-B*35 and B*49 alleles were strongly enriched among Armanis and Turkamans, respectively. A total of 13 HLA-C alleles were identified across the population, all of which were present in the Fars subpopulation. HLA-C*03 and C*04 were the only HLA-C alleles identified among the Bandari subpopulation. HLA-DRB1*08 was not detected in any subpopulation other than Fars. HLA-DRB1*16 was significantly enriched among Bandaris. These data have practical significance in anthropological studies, disease association investigations and bone marrow transplantation.
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http://dx.doi.org/10.3233/HAB-220004DOI Listing
January 2022

Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients.

Cytokine 2022 May 4;153:155849. Epub 2022 Mar 4.

Critical Care Quality Improvement Research Center, Loghman Hakin Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Critical Care Fellowship, Department of Anesthesiology, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.
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http://dx.doi.org/10.1016/j.cyto.2022.155849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894869PMC
May 2022

The Interaction Between Non-Coding RNAs and Calcium Binding Proteins.

Front Oncol 2022 4;12:848376. Epub 2022 Mar 4.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Calcium binding proteins (CBP) are a group of proteins mediating the effects of calcium on cellular functions. These proteins can regulate calcium levels inside the cells and contribute in several cellular functions through transporting this ion across cell membranes or decoding related signals. Recent studies have shown that several non-coding RNAs interact with CBPs to affect their expression or activity. The interactions between these transcripts and CBPs have implications in the pathoetiology of human disorders, including both neoplastic and non-neoplastic conditions. In the current review, we describe the interactions between three classes of non-coding RNAs (long non-coding RNAs, circular RNAs, and microRNAs) and a number of CBPs, particularly CAB39, S100A1, S100A4, S100A7 and S100P. This kind of interaction has been verified in different pathological contexts such as drug-induced cardiotoxicity, osteoblasts cytotoxicity, acute lung injury, myocardial ischemia/reperfusion injury, proliferative diabetic retinopathy, glomerulonephritis, as well as a wide array of neoplastic conditions.
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http://dx.doi.org/10.3389/fonc.2022.848376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934394PMC
March 2022

Expression of BDNF-Associated lncRNAs in Parkinson's disease.

Metab Brain Dis 2022 Apr 19;37(4):901-909. Epub 2022 Mar 19.

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

Decreased level of neurotrophic factor brain-derived neurotrophic factor (BDNF) has been supposed to participate in the pathoetiology of Parkinson's disease (PD). However, the underlying mechanisms of its dysregulation and the functional network between this factor and other transcripts have not been elucidated. In the current study, we measured expressions of BDNF, and four related long non-coding RNAs, namely BDNF-AS, MIR137HG, MIAT and PNKY in blood of PD patients and normal controls to find their expression levels in these patients and propose a possible mechanism for dysregulation of BDNF in PD patients. Notably, we detected down-regulation of all transcripts in the circulation of PD patients compared with controls. There was no significant difference in expression of either gene between male and female PD patients or patients receiving L-Dopa versus those receiving other drugs. Expression of none of genes was correlated with age, disease duration, disease stage, MMSE or UPDRS. Dynamic principal component analysis showed that expression levels of these genes almost clearly separated samples collected from healthy controls and PD patients into their respective groups. This suggests that the observed lncRNAs differences are associated with the pathophysiology of PD, and these lncRNAs might constitute an important biomarker signature for PD.
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http://dx.doi.org/10.1007/s11011-022-00946-1DOI Listing
April 2022

The Role of Circular RNAs in the Carcinogenesis of Bladder Cancer.

Front Oncol 2022 28;12:801842. Epub 2022 Feb 28.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Circular RNAs (circRNAs) are a group of transcripts with enclosed configurations which can regulate gene expression. These transcripts have important roles in normal development and in the pathogenesis of disorders. Recent evidence has supported involvement of circRNAs in the development of bladder cancer. Several circRNAs such as circ_0058063, hsa-circRNA-403658, circPDSS1, circCASC15, circRNA-MYLK, and circRNA_103809 have been upregulated in bladder cancer samples. On the other hand, hsa_circ_0137606, BCRC-3, circFUT8, hsa_circ_001598, circSLC8A1, hsa_circ_0077837, hsa_circ_0004826, and circACVR2A are among downregulated circRNAs in bladder cancer. Numerous circRNAs have diagnostic or prognostic value in bladder cancer. In this review, we aim to outline the latest findings about the role of circRNAs in bladder cancer and introduce circRNAs for further investigations as therapeutic targets.
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http://dx.doi.org/10.3389/fonc.2022.801842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918517PMC
February 2022

DLX6-AS1: A Long Non-coding RNA With Oncogenic Features.

Front Cell Dev Biol 2022 25;10:746443. Epub 2022 Feb 25.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with characteristic size of more than 200 nucleotides. An increasing number of lncRNAs have been found to be dysregulated in many human diseases particularly cancer. However, their role in carcinogenesis is not precisely understood. DLX6-AS1 is an lncRNAs which has been unveiled to be up-regulated in various number of cancers. In different cell studies, DLX6-AS1 has shown oncogenic role promoting oncogenic phenotype of cancer cell lines. Increase in tumor cell proliferation, migration, invasion, and EMT while suppressing apoptosis in cancer cells are the effects of DLX6-AS1 in development and progression of cancer. In the majority of cell experiment, mediator miRNAs have been identified which are sponged and negatively regulated by DLX6-AS1, and they in turn regulate expression of a number of transcription factors, eventually affecting signaling pathways involved in carcinogenesis. These pathways form axes through which DLX6-AS1 promotes carcinogenicity of cancer cells. Xenograft animal studies, also have confirmed enhancing effect of DLX6-AS1 on tumor growth and metastasis. Clinical evaluations in cancerous patients have also shown increased expression of DLX6-AS1 in tumor tissues compared to healthy tissues. High DLX6-AS1 expression has shown positive association with advanced clinicopathological features in cancerous patients. Survival analyses have demonstrated correlation between high DLX6-AS1 expression and shorter survival. In cox regression analysis, DLX6-AS1 has been found as an independent prognostic factor for patients with various types of cancer.
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http://dx.doi.org/10.3389/fcell.2022.746443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916230PMC
February 2022

Abnormal pattern of vitamin D receptor-associated genes and lncRNAs in patients with bipolar disorder.

BMC Psychiatry 2022 03 12;22(1):178. Epub 2022 Mar 12.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Bipolar disorder (BD) is a multifactorial condition. Several signaling pathways affect development of this disorder. With the purpose of exploring the role of vitamin D receptor (VDR) signaling in this disorder, we measured expression of selected mRNA coding genes and long non-coding RNAs (lncRNAs) in this pathway in patients versus normal subjects.

Methods: We measured expression of VDR-associated lncRNAs and mRNAs (SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1) in the peripheral blood of BD patients vs. healthy individuals.

Results: Expression of SNHG6 was significantly higher in cases vs. controls (Posterior beta = 1.29, P value < 0.0001. Subgroup analysis by sex revealed significant results in both subgroups (P value < 0.0001 and P value = 0.023 for males and females, respectively). Expression of CYP27B1 was up-regulated in cases vs. controls (Posterior beta = 0.415, P < 0.0001). Such pattern was also detected among males (P < 0.0001), but not females (P = 0.419). Similarly, MALAT1 and Linc00346 were up-regulated in total cases vs. controls (Posterior beta = 0.694, P < 0.0001 and Posterior beta = 0.4, P = 0.012, respectively) and in male cases compared with male controls (Posterior beta = 0.712, P < 0.0001 and Posterior beta = 0.41, P value = 0.038, respectively). Expression of VDR was up-regulated in total cases compared with controls (Posterior beta = 0.683, P value = 0.001). Finally, expression of Linc00511 was not different between groups. MALAT1, SNHG6, CYP27B1, VDR and Linc00346 had AUC values of 0.95, 0.94, 0.91, 0.85 and 0.83 in differentiation of male patients from controls, respectively.

Conclusion: The current study suggests VDR-associated genes as possible markers for BD.
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http://dx.doi.org/10.1186/s12888-022-03811-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918307PMC
March 2022

The role of circular RNAs in pancreatic cancer: new players in tumorigenesis and potential biomarkers.

Pathol Res Pract 2022 Apr 2;232:153833. Epub 2022 Mar 2.

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

Circular RNAs (circRNAs) are a newly identified class of non-coding RNAs (ncRNAs) which show different structure compared to other RNAs in terms of their covalently closed ends. To date, a huge number of circRNAs have been identified in various species and also several databases have been created for storing and providing accessibility to retrieved data on identified circRNAs. They are produced by back-splicing from mainly protein-coding genes. Same to other ncRNAs, circRNAs have been found to play role in gene regulation via interaction with other biomolecules like nucleic acids, proteins and microRNAs (miRNAs). They are involved in different physiological processes like vascular functions, brain and embryonic development, regulation of metabolism, cell cycle control and response to cellular stress. Dysregulation of circRNAs have been associated with many types of human diseases like cardiovascular diseases, immune diseases, neurologic diseases, diabetes and particularly various types of cancer. In this review, we have a look to the cellular experiments conducted on the role of circRNAs in the pancreatic cancer. Two cellular behaviors of two categories of circRNAs including up-regulated and down-regulated transcripts have been reviewed in pancreatic cancer. Furthermore, their potential application in diagnosis and prognosis of pancreatic cancer has been summarized. The results show circRNAs are potential diagnostic and prognostic biomarkers of pancreatic cancer.
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http://dx.doi.org/10.1016/j.prp.2022.153833DOI Listing
April 2022

The importance of miRNA-630 in human diseases with an especial focus on cancers.

Cancer Cell Int 2022 Mar 5;22(1):105. Epub 2022 Mar 5.

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

miR-630 is encoded by MIR630 gene (NC_000015.10) on 15q24.1. This miRNA is mostly associated with cytokine signaling in immune system. Several neoplastic as well as non-neoplastic conditions have been linked with dysregulation of miR-630. It is an oncogenic miRNA in renal cell carcinoma, multiple myeloma, colorectal cancer, acute lymphoblastic leukemia, ovarian cancer and prostate cancer. On the other hand, it is a putative tumor suppressor miRNA in lung, cervical, breast, thyroid and esophageal tissues. In a number of other tissues, data regarding the role of miR-630 in the carcinogenesis is conflicting. Expression levels of miR-630 can be used as markers for prediction of cancer course. Moreover, miR-630 can influence response to chemoradiotherapy. This miRNA is also involved in the pathoetiology of IgA nephropathy, obstructive sleep apnea, age-related nuclear cataract and vitiligo. In the present review, we discuss the role of miR-630 in these conditions.
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http://dx.doi.org/10.1186/s12935-022-02531-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897855PMC
March 2022

Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

Mol Cancer 2022 03 3;21(1):64. Epub 2022 Mar 3.

Institute of Human Genetics, Jena University Hospital, Jena, Germany.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges facing CRISPR/Cas9-based treatments and proposed strategies to overcome these limitations, for further enhancing this revolutionary novel therapeutics to improve long-term treatment outcome human health.
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http://dx.doi.org/10.1186/s12943-021-01487-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892709PMC
March 2022

The effects of Ginsenosides on PI3K/AKT signaling pathway.

Mol Biol Rep 2022 Feb 27. Epub 2022 Feb 27.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions.
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http://dx.doi.org/10.1007/s11033-022-07270-yDOI Listing
February 2022

The emerging role non-coding RNAs in B cell-related disorders.

Cancer Cell Int 2022 Feb 22;22(1):91. Epub 2022 Feb 22.

Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs and microRNAs have recently attained much attention regarding their role in the development of B cell lineage as well as participation in the lymphomagenesis. These transcripts have a highly cell type specific signature which endows them the potential to be used as biomarkers for clinical situations. Aberrant expression of several non-coding RNAs has been linked with B cell malignancies and immune related disorders such as rheumatoid arthritis, systemic lupus erythematous, asthma and graft-versus-host disease. Moreover, these transcripts can alter response of immune system to infectious conditions. miR-7, miR-16-1, miR-15a, miR-150, miR-146a, miR-155, miR-212 and miR-132 are among microRNAs whose role in the development of B cell-associated disorders has been investigated. Similarly, SNHG14, MALAT1, CRNDE, AL133346.1, NEAT1, SMAD5-AS1, OR3A4 and some other long non-coding RNAs participate in this process. In the current review, we describe the role of non-coding RNAs in B cell malignancies.
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http://dx.doi.org/10.1186/s12935-022-02521-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862212PMC
February 2022

A review on the role of PCA3 lncRNA in carcinogenesis with an especial focus on prostate cancer.

Pathol Res Pract 2022 Mar 11;231:153800. Epub 2022 Feb 11.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The prostate cancer antigen 3 (PCA3) is a long non-coding RNA (lncRNA) with high level of specificity for prostate cancer. This lncRNA has fundamental effects in the prostate carcinogenesis through modulation of expression of miR-132-3p, miR-1261, SREBP1, PRKD3 and LAP2α as well as regulation of p53 signaling. Expression of PCA3 in prostate cancer cells can be enhanced by Snail. Moreover, in vitro studies have documented up-regulation of PCA3 in three other types of neoplastic cells, namely those being originated from choriocarcinoma, ovarian carcinoma and thyroid carcinoma. The diagnostic value of PCA3 in differentiation of prostate cancer from benign prostate hyperplasia has been assessed in different studies. Studies aimed at identification of diagnostic power of PCA3 in prostate cancer using receiver operating characteristic curves have reported area under curve values ranging from 0.66 to 0.86. In the current review, we describe the role of PCA3 in the carcinogenesis particularly in the pathoetiology of prostate cancer. Moreover, we review the results of studies appraising diagnostic value of this lncRNA in prostate cancer.
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http://dx.doi.org/10.1016/j.prp.2022.153800DOI Listing
March 2022

Emerging role of non-coding RNAs in the regulation of KRAS.

Cancer Cell Int 2022 Feb 9;22(1):68. Epub 2022 Feb 9.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The Kirsten ras oncogene KRAS is a member of the small GTPase superfamily participating in the RAS/MAPK pathway. A single amino acid substitution in KRAS gene has been shown to activate the encoded protein resulting in cell transformation. This oncogene is involved in the malignant transformation in several tissues. Notably, numerous non-coding RNAs have been found to interact with KRAS protein. Such interaction results in a wide array of human disorders, particularly cancers. Orilnc1, KIMAT1, SLCO4A1-AS1, LINC01420, KRAS1P, YWHAE, PART1, MALAT1, PCAT-1, lncRNA-NUTF2P3-001 and TP53TG1 are long non-coding RNAs (lncRNAs) whose interactions with KRAS have been verified in the context of cancer. miR-143, miR-96, miR-134 and miR-126 have also been shown to interact with KRAS in different tissues. Finally, circITGA7, circ_GLG1, circFNTA and circ-MEMO1 are examples of circular RNAs (circRNAs) that interact with KRAS. In this review, we describe the interaction between KRAS and lncRNAs, miRNAs and circRNAs, particularly in the context of cancer.
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http://dx.doi.org/10.1186/s12935-022-02486-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8827276PMC
February 2022
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