Publications by authors named "Bashdar Mahmud Hussen"

21 Publications

  • Page 1 of 1

LncRNA signature in colorectal cancer.

Pathol Res Pract 2021 Apr 7;222:153432. Epub 2021 Apr 7.

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

Colorectal cancer (CRC) is among the most frequent cancers and is associated with high mortality particularly when being diagnosed in advanced stages. Although several environmental and intrinsic risk factors have been identified, the underlying cause of CRC is not clear in the majority of cases. Several studies especially in the recent decade have pointed to the role of epigenetic factors in this kind of cancer. Long non-coding RNAs (lncRNAs) as important contributors in the epigenetic mechanisms are involved in the initiation, progression and metastasis of CRC. Tens of oncogenic lncRNAs and a lower number of tumor suppressor lncRNAs have been recently identified to be dysregulated in CRC cells and tissues. Notably, expressions of a number of these transcripts have been dysregulated in serum samples of CRC patients, providing a non-invasive route for detection of this kind of cancer. The involvement of lncRNAs in the regulation of autophagy has provided them the ability to modulate response of CRC cells to chemotherapeutic modalities. In the current manuscript, we review the studies which evaluated the role of lncRNAs in the pathogenesis and progression of CRC to appraise their application as diagnostic/ prognostic markers.
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http://dx.doi.org/10.1016/j.prp.2021.153432DOI Listing
April 2021

The Impact of Non-coding RNAs in the Epithelial to Mesenchymal Transition.

Front Mol Biosci 2021 26;8:665199. Epub 2021 Mar 26.

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

Epithelial to mesenchymal transition (EMT) is a course of action that enables a polarized epithelial cell to undertake numerous biochemical alterations that allow it to adopt features of mesenchymal cells such as high migratory ability, invasive properties, resistance to apoptosis, and importantly higher-order formation of extracellular matrix elements. EMT has important roles in implantation and gastrulation of the embryo, inflammatory reactions and fibrosis, and transformation of cancer cells, their invasiveness and metastatic ability. Regarding the importance of EMT in the invasive progression of cancer, this process has been well studies in in this context. Non-coding RNAs (ncRNAs) have been shown to exert critical function in the regulation of cellular processes that are involved in the EMT. These processes include regulation of some transcription factors namely SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47, modulation of chromatin configuration, alternative splicing, and protein stability and subcellular location of proteins. In the present paper, we describe the influence of ncRNAs including microRNAs and long non-coding RNAs in the EMT process and their application as biomarkers for this process and cancer progression and their potential as therapeutic targets.
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http://dx.doi.org/10.3389/fmolb.2021.665199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033041PMC
March 2021

The role of miRNAs and lncRNAs in conferring resistance to doxorubicin.

J Drug Target 2021 Apr 15:1-21. Epub 2021 Apr 15.

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

Doxorubicin is a chemotherapeutic agent that inhibits topoisomerase II, intercalates within DNA base pairs and results in oxidative DNA damage, thus inducing cell apoptosis. Although it is effective in the treatment of a wide range of human cancers, the emergence of resistance to this drug can increase tumour growth and impact patients' survival. Numerous molecular mechanisms and signalling pathways have been identified that induce resistance to doxorubicin via stimulation of cell proliferation, cell cycle switch and preclusion of apoptosis. A number of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have also been identified that alter sensitivity to doxorubicin. Understanding the particular impact of these non-coding RNAs in conferring resistance to doxorubicin has considerable potential to improve selection of chemotherapeutic regimens for cancer patients. Moreover, modulation of expression of these transcripts is a putative strategy for combating resistance. In the current paper, the influence of miRNAs and lncRNAs in the modification of resistance to doxorubicin is discussed.
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http://dx.doi.org/10.1080/1061186X.2021.1909052DOI Listing
April 2021

MicroRNA: A signature for cancer progression.

Biomed Pharmacother 2021 Mar 23;138:111528. Epub 2021 Mar 23.

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

MicroRNAs (miRNAs) are a group of small non-coding RNAs that post-transcriptionally control expression of genes by targeting mRNAs. miRNA alterations partake in the establishment and progression of different types of human cancer. Consequently, expression profiling of miRNA in human cancers has correlations with cancer detection, staging, progression, and response to therapies. Particularly, amplification, deletion, abnormal pattern of epigenetic factors and the transcriptional factors that mediate regulation of primary miRNA frequently change the landscape of miRNA expression in cancer. Indeed, changes in the quantity and quality of miRNAs are associated with the initiation of cancer, its progression and metastasis. Additionally, miRNA profiling has been used to categorize genes that can affect oncogenic pathways in cancer. Here, we discuss several circulating miRNA signatures, their expression profiles in different types of cancer and their impacts on cellular processes.
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http://dx.doi.org/10.1016/j.biopha.2021.111528DOI Listing
March 2021

The interaction between miRNAs/lncRNAs and Notch pathway in human disorders.

Biomed Pharmacother 2021 Mar 17;138:111496. Epub 2021 Mar 17.

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

Notch pathway is a signaling cascade with important impacts on cell proliferation, differentiation, developmental processes and tissue homeostasis. This pathway also regulates stem cell properties, thus being involved in both normal developmental processes and metastatic capacity of cancer cells. Lots of lncRNAs and miRNAs have been recognized that control Notch pathway at some levels or their expression is regulated by this pathway. FOXD2-AS1, MEG3, ANRIL, linc-OIP5, lincRNA-p21, CBR3-AS1, HOTAIR, PVT1 and GAS5 are among lncRNAs that interact with Notch signaling. miR-19, miR-21, miR-33a, miR-8/200, miR-34a, miR-146a, miR-37, miR-100, miR-107 and several other miRNAs have functional interplay with this signaling cascade. In the present review article, we have illuminated the interplay between lncRNAs/miRNAs and Notch pathway in two distinct contexts i.e. cancers and non-neoplastic conditions.
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http://dx.doi.org/10.1016/j.biopha.2021.111496DOI Listing
March 2021

A Diagnostic Panel for Acquired Immune-Mediated Polyneuropathies Based on the Expression of lncRNAs.

Front Immunol 2021 23;12:643615. Epub 2021 Feb 23.

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

Long non-coding RNAs (lncRNAs) have been shown to alter immune responses, thus contributing to the pathobiology of autoimmune conditions. We investigated the expression levels of ANRIL, PICART1, MALAT1, CCAT1, CCAT2, and CCHE1 lncRNAs in acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP). ANRIL, PICART1, MALAT1, CCAT1, CCAT2, and CCHE1 lncRNAs were significantly downregulated in individuals with both AIDP and CIDP compared with unaffected individuals. Gender-based comparisons also verified such downregulations in both male and female subjects compared with sex-matched unaffected controls for all lncRNAs. There was no significant difference in the expression of any of the lncRNAs between cases with AIDP and cases with CIDP. While the expression levels of ANRIL and PICART1 were significantly correlated in healthy subjects (r = 0.86, = 8.5E-16), similar analysis in cases with AIDP and CIDP revealed no significant correlation. The most robust correlation among patients was detected between ANRIL and MALAT1 lncRNAs (r = 0.59, = 3.52E-6). ANRIL, MALAT1, and PICART1 had the diagnostic power of 0.96, 0.94, and 0.92 in distinguishing between cases with CIDP and controls, respectively. A combination of all lncRNAs resulted in 0.95 diagnostic power with a sensitivity of 0.85 and specificity of 0.96 for this purpose. Diagnostic power values of these lncRNAs in differentiation between cases with AIDP and controls were 0.98, 0.95, and 0.93, respectively. The combinatorial diagnostic power reached 0.98 for differentiation between cases with AIDP and controls. The six-lncRNA panel could differentiate combined cases with AIDP and CIDP from controls with area under the curve (AUC), sensitivity, and specificity values of 0.97, 0.90, and 0.96, respectively. Collectively, the lncRNA panel is suggested as a sensitive and specific diagnostic panel for acquired immune-mediated polyneuropathies.
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http://dx.doi.org/10.3389/fimmu.2021.643615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940672PMC
February 2021

BCYRN1: An oncogenic lncRNA in diverse cancers.

Pathol Res Pract 2021 Apr 16;220:153385. Epub 2021 Feb 16.

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

Brain cytoplasmic 200 (BC200) or alternatively named as brain cytoplasmic RNA 1 (BCYRN1) is a long non-coding RNA (lncRNA) primarily identified in the neurons. In addition to its participation in the pathogenesis of neurodegenerative disorders, it partake in the carcinogenesis process. Numerous in vitro studies have reported elevation of expression of BCYRN1 in cancer cell lines. Short hairpin-RNA-mediated silencing of BCYRN1 has attenuated growth of tumors in the animal models. Independent studies in esophageal squamous cell cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma and non-small cell lung cancer have demonstrated association between elevated BCYRN1 levels and poor survival of patients. Taken together, BCYRN1 is an appropriate candidate for targeted therapies in the field of cancer.
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http://dx.doi.org/10.1016/j.prp.2021.153385DOI Listing
April 2021

An update on the role of long non-coding RNAs in the pathogenesis of breast cancer.

Pathol Res Pract 2021 Mar 9;219:153373. Epub 2021 Feb 9.

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

Breast cancer is the most frequent female malignancy. This malignancy has diverse clinical and molecular subtypes with different prognoses. Dysregulation of long non-coding RNAs (lncRNAs) not only participates in the development of breast cancer, but also affects the clinical course and prognosis of this type of cancer. Hundreds of studies have shown up-regulation or down-regulation of lncRNAs in breast cancer samples or serum samples of affected individuals suggesting these RNA molecules as diagnostic markers for breast cancer. Different anticancer agents such as trastuzumab, lapatinib, doxorubicin, hydroxyurea, docetaxel, 5-fluorouracil and 6-thioguanine affect expression profile of lncRNAs. In the present article, we review the results of investigations about the role of lncRNAs in the evolution of breast cancer.
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http://dx.doi.org/10.1016/j.prp.2021.153373DOI Listing
March 2021

MicroRNA signature in liver cancer.

Pathol Res Pract 2021 Mar 9;219:153369. Epub 2021 Feb 9.

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

Liver cancer is the 7 utmost frequent neoplasm and the 4 principal source of cancer deaths. This malignancy is linked with several environmental and lifestyle-related factors emphasizing the role of epigenetics in its pathogenesis. MicroRNAs (miRNAs) have been regarded as potent epigenetic mechanisms partaking in the pathogenesis of liver cancer. Dysregulation of miRNAs has been related with poor outcome of patients with liver cancer. In the current manuscript, we provide a concise review of the results of recent studies about the role of miRNAs in the progression of liver cancer and their diagnostic and prognostic utility.
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http://dx.doi.org/10.1016/j.prp.2021.153369DOI Listing
March 2021

Emerging role of microRNAs in the pathogenesis of amyotrophic lateral sclerosis.

Metab Brain Dis 2021 Feb 19. Epub 2021 Feb 19.

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

Amyotrophic lateral sclerosis (ALS) is a deadly motor neuron disease (MND) and the most frequent MND in adults. ALS is recognized by degenerative alterations in both upper and lower motor neurons. This disorder is classified to familial and sporadic classes. Disease-causing mutations in SOD1, C9ORF72, FUS, and TARDBP have been recognized in familial ALS cases. However, in spite of conduction of several genetic association studies, heritable genetic risk elements in sporadic have not been identified completely. Several miRNAs have been dysregulated in the serum samples or brain tissues of ALS patients. Moreover, a number of miRNAs have been suggested as putative biomarkers for sporadic ALS. In the current manuscript, we review of miRNAs in the development of ALS.
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http://dx.doi.org/10.1007/s11011-021-00697-5DOI Listing
February 2021

A review on the role of oncogenic lncRNA OIP5-AS1 in human malignancies.

Biomed Pharmacother 2021 May 15;137:111366. Epub 2021 Feb 15.

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

OIP5-AS1 is a long non-coding transcript with high expression in nervous system, but crucial functions in the neoplastic transformation. This lncRNA partake in the regulation of cell cycle transition at different points. Moreover, it acts a competing endogenous RNA for tens of microRNAs among them are miR-338-3p, miR-204-5p, miR-641, miR-422a, miR-367-3p, miR-153-3p, miR-186, miR-369-3p, miR-137, miR-342-3p, miR‑429, miR-3163, miR-363-3p, miR-186a-5p, hsa-miR-26a-3p, miR‑300, miR-217, miR-378a-3p and miR-448. OIP5-AS1 influence the carcinogenesis via different routes among them is modulation of epithelial-mesenchymal transition. Expression of OIP5-AS1 has been elevated in nearly all kinds of neoplastic tissues except for multiple myeloma. Moreover, in bladder, gastric cancer and lung cancers, assessment of its expression in clinical samples has led to conflicting results. In the current paper, we have provided a comprehensive collection of research papers that evaluated function of OIP5-AS1 in diverse cancer types.
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http://dx.doi.org/10.1016/j.biopha.2021.111366DOI Listing
May 2021

Expression of T helper 1-associated lncRNAs in breast cancer.

Exp Mol Pathol 2021 04 12;119:104619. Epub 2021 Feb 12.

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

Interferon gamma (IFN-gamma)-associated genes participate in the pathobiology of cancer and response of patients to immunotherapeutic modalities. This cytokine is regarded as a hallmark of T helper 1 type responses. In the current study, we estimated expression of this gene and a number of genes/ long non-coding RNAs (IFNG.AS001 and IFNG.AS003, AC007278.2 and AC007278.3 and IL18R1) which are encoded from proximal genomic regions to IFNG in a larger cohort of Iranian patients with breast cancer. Both IFNG.AS001 and IFNG.AS003 were up-regulated in breast cancer tissues compared with nearby non-cancerous tissues (Ratios of Mean Expressions = 5.62 and 5.88, P values = 1.28E-03 and 1.47E-03, respectively). Finally, IL18R1 was over-expressed in breast cancer tissues compared with nearby non-cancerous tissues (Ratio of Mean Expressions = 9.43, P values = 3.14E-03). Expression of AC007278.3 was associated with breast feeding duration (P value = 2.65E-02). Positive significant correlations were detected between expression levels of all genes in both sets of samples. The most robust correlation in the nearby non-cancerous tissues was detected between IFNG-AS003 and AC007278.2 (r = 088, P value = 5.19E-23). In the tumoral tissues, the strongest correlation was found between IFNG-AS001 and IL18R1 (r = 0.86, P value = 3.79E-15). AC007278.3 had the best diagnostic power among the assessed genes (AUC = 0.82). Both AC007278.2 and AC007278.3 were reported to be specific markers for differentiation of tumor tissues from nearby non-cancerous tissues. Combination of expression levels of genes increased specificity, sensitivity and AUC values to 0.97, 0.89 and 0.95, respectively. The current study accentuates the role of IFNG-associated genes in the pathogenesis of breast cancer.
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http://dx.doi.org/10.1016/j.yexmp.2021.104619DOI Listing
April 2021

Altered IFN-γ Levels after Treatment of Epileptic Patients with Omega-3 Fatty Acids.

J Mol Neurosci 2021 Feb 12. Epub 2021 Feb 12.

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

Epilepsy is a frequent chronic disorder of the brain characterized by intermittent epileptic seizures caused by hypersynchronous discharge of neurons in the brain. Studies have reported the role of cytokines in the pathogenesis of epilepsy, and a number of investigations have shown decreased levels of omega-3 fatty acids in epileptic patients. We investigated differences in serum levels of two cytokines, transforming growth factor (TGF)-β and interferon (IFN)-γ, in 40 epileptic cases prior to and after treatment with omega-3 fatty acids. IFN-γ levels were significantly increased after the 16-week treatment period (P < 0.001). However, TGF-β levels remained unchanged (P = 0.14). Omega-3 fatty acid treatment may alter the immune response in epileptic patients. This should be considered in prescription of omega-3 fatty acid supplements in these patients. Future studies with larger sample sizes should verify the results of the current study.
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http://dx.doi.org/10.1007/s12031-021-01804-yDOI Listing
February 2021

The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis.

Respir Res 2021 Feb 12;22(1):53. Epub 2021 Feb 12.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Several risk factors such as smoking, air pollution, inhaled toxins, high body mass index and infectious agents are involved in the pathogenesis of IPF. In the present study, this meta-analysis study investigates the prevalence of viral and bacterial infections in the IPF patients and any possible association between these infections with pathogenesis of IPF.

Methods: The authors carried out this systematic literature review from different reliable databases such as PubMed, ISI Web of Science, Scopus and Google Scholar to December 2020.Keywords used were the following "Idiopathic pulmonary fibrosis", "Infection", "Bacterial Infection" and "Viral Infection", alone or combined together with the Boolean operators "OR", "AND" and "NOT" in the Title/Abstract/Keywords field. Pooled proportion and its 95% CI were used to assess the prevalence of viral and bacterial infections in the IPF patients.

Results: In this systematic review and meta-analyses, 32 studies were selected based on the exclusion/inclusion criteria. Geographical distribution of included studies was: eight studies in American people, 8; in European people, 15 in Asians, and one in Africans. The pooled prevalence for viral and bacterial infections w ere 53.72% (95% CI 38.1-69.1%) and 31.21% (95% CI 19.9-43.7%), respectively. The highest and lowest prevalence of viral infections was HSV (77.7% 95% CI 38.48-99.32%), EBV (72.02%, 95% CI 44.65-90.79%) and Influenza A (7.3%, 95% CI 2.66-42.45%), respectively. Whereas the highest and lowest prevalence in bacterial infections were related to Streptococcus sp. (99.49%, 95% CI 96.44-99.9%) and Raoultella (1.2%, 95% CI 0.2-3.08%), respectively.

Conclusions: The results of this review were confirmed that the presence of viral and bacterial infections are the risk factors in the pathogenesis of IPF. In further analyses, which have never been shown in the previous studies, we revealed the geographic variations in the association strengths and emphasized other methodological parameters (e.g., detection method). Also, our study supports the hypothesis that respiratory infection could play a key role in the pathogenesis of IP.
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http://dx.doi.org/10.1186/s12931-021-01650-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880524PMC
February 2021

The critical roles of lncRNAs in the development of osteosarcoma.

Biomed Pharmacother 2021 Mar 1;135:111217. Epub 2021 Feb 1.

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

Osteosarcoma is rare malignancy of childhood and adolescence, with high morbidity and mortality despite accomplishment of diverse therapeutic modalities. Identification of the underlying mechanism of osteosarcoma evolution would help in better management of this rare malignancy. Lots of investigations have described abnormal regulation of long non-coding RNAs (lncRNAs) in clinical specimens of osteosarcoma and the established cell lines. This malignancy has been associated with over-expression of TUG1, LOXL1-AS1, MIR100HG, NEAT1, HULC, ANRIL and a number of other lncRNAs, while under-expression of lots of lncRNAs including LncRNA-p21, FER1L4, GAS5, LncRNA NR_136400 and LINC-PINT. Expression amounts of LUCAT1, LINC00922, SNHG12, FOXC2-AS1 and OIP5-AS1 lncRNAs have been associated with response to a number of chemotherapeutic agents. Taken together, lncRNAs are possible targets for proposing novel advanced therapeutic modalities for osteosarcoma.
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http://dx.doi.org/10.1016/j.biopha.2021.111217DOI Listing
March 2021

Opposite trends of GAS6 and GAS6-AS expressions in breast cancer tissues.

Exp Mol Pathol 2021 02 24;118:104600. Epub 2020 Dec 24.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Growth arrest-specific gene 6 (GAS6) is a growth factor-like cytokine whose function is related with vitamin K. This protein interacts with receptor tyrosine kinase proteins such as Tyro3, Axl, and TAM Receptor family, therefore affecting the tumorigenic processes via different mechanisms. GAS6-antisense 1 (GAS6-AS1) is a long non-coding RNAs (lncRNAs) that is transcribed from a genomic regions nearby GAS6. This lncRNA is also implicated in the pathobiology of cancer. We intended to judge the role of GAS6 and GAS6-AS1 in the pathogenesis of breast cancer through appraisal of their expression levels in breast cancer tissues and their paired neighboring non-cancerous samples. Expression of GAS6 was up-regulated in breast cancer tissues compared with neighboring tissues (Ratio of Mean Expressions = 2.18, P value = 4.98E-02). On the other hand, expression of GAS6-AS1 was down-regulated in breast tumor tissues compared with controls (Ratio of Mean Expressions = 0.37, P value = 4.26E-03). There were substantial correlations between expression levels GAS6 and GAS6-AS1 in non-cancerous tissues (r = 0.74, P value = 1.47e-13) and cancer tissues (r = 0.85, P value = 2.28e-20). Expression of GAS6-AS was associated with progesterone receptor status (P value = 1.36E-02). However, expressions of this gene and the sense transcript were not linked with any other clinical or demographic variable. Taken together, GAS6 and GAS6-AS1 might partake in the development of breast cancer.
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http://dx.doi.org/10.1016/j.yexmp.2020.104600DOI Listing
February 2021

The role of HPV gene expression and selected cellular MiRNAs in lung cancer development.

Microb Pathog 2021 Jan 7;150:104692. Epub 2020 Dec 7.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background: The high mortality rate of lung cancer can be justified that strong need to explore new aspect of tumor biology. Human papillomavirus (HPV) has been detected as risk factor for the development of lung cancer. The aim of this study was to determine the role of HPV and cellular/miRNAs genes expression in the epithelial-mesenchymal transition (EMT) and development of lung cancer.

Methods: In this case-control study, 109 lung cancer tissue and 52 controls were included. We analyzed the presence of HPV infection, its genotypes (in positive samples) and the expression of viral genes (E2, E6 and E7). Also, We examined the expression of celluar factors including (a) p53 and retinoblastoma (Rb) (as anti-carcinogenic genes), (b) EMT related genes, (c) selected miRNAs.

Results: Our results reported 51.4% and 23.1% of HPV genome in tumor tissues and control tissues samples, respectively. There was a significant association between the HPV positive status and lung cancer (OR = 3.26, 95% C.I = 1.47-7.02, P = 0.001). HPV type 16 was the most prevalent genotype in tissues. The expression of p53, RB, TIMP1, CCNG-1, E-cad and PTPN13 were decreased while MMP-2 and N-cad were increased in HPV-positive tumor/control tissues compared to HPV-negative tissues. Also, among miRNAs, let-7, miR-23, miR-34, miR-125, miR-146 were downregulated and miR-20, miR-424 were upregulated in HPV-positve tissues compared to HPV-negative tissues.

Conclusion: This study demonstrated that HPV infection and interaction with cellular genes and miRNAs promote EMT which involved in the lung cancer development.
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http://dx.doi.org/10.1016/j.micpath.2020.104692DOI Listing
January 2021

Down-regulation of Survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family.

Toxicol Appl Pharmacol 2020 12 7;409:115331. Epub 2020 Nov 7.

Department of Biology, College of Education, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.

Ciprofloxacin derivatives belong to a family of antibiotics called fluoroquinolones. Recently, these compounds have been recommended for the treatment of cancer. In the present study, we assessed the cytotoxicity of several new synthetic ciprofloxacin derivatives and the apoptosis-inducing activity of the most efficient derivative in two human myeloid leukemia K562 and KG1-a cell lines. Among the prepared ciprofloxacin derivatives, 1-cyclopropyl-7-(4-(2-((3,7-dimethyloct-6-en-1-yl)oxy)-2-oxoethyl)piperazin-1-yl)-6-fluoro-4-oxo-1,4dihydroquinoline-3-carboxylic acid (4-DMOCP) was more active compound with IC50 of 19.56 and 22.13 μM for K562 and KG1-a, respectively. Apoptotic activity of the 4-DMOCP was examined morphologically through Hoechst 33258 staining, Annexin V/PI double staining, and caspase-3 activity assays. Changes in the expression level of some apoptosis-related genes and protein, including Bcl-2, Bax, Survivin, p53, Caspase-8 and Caspase-9 were evaluated by the real-time quantitative PCR (qRT PCR) and western blotting. The qRT PCR analysis showed that 4-DMOCP induces apoptosis in both cell lines via the down-regulation of Survivin and Bcl2, up-regulation of caspase-8 and -9, as well as a time-dependent increase in the Bax/Bcl2 transcripts. The mRNA level of p53 was also increased in both cell lines. In addition, western blot analysis revealed that treatment with the compound, down-regulated the protein expression levels of Bcl2 and Survivin and up-regulated the protein level of Bax in both cell lines. These findings suggest that these new compounds can be good candidates for the treatment of acute and chronic myeloid leukemia.
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http://dx.doi.org/10.1016/j.taap.2020.115331DOI Listing
December 2020

Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis.

Microb Pathog 2021 Mar 18;152:104576. Epub 2020 Oct 18.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The aim of this study is to address the role of HPV in prostate cancer (PCa) development through the inducement of resistance to anoikis.

Methods: In this case-control study, prostate tissues and blood samples were collected from 116 individuals, including 72 cases with PCa and 44 non-malignant prostate tissue samples as a control group. The expression level of HPV genes (E2, E6, and E7) and cellular genes including anti-apoptotic mediators (Bcl-2 and survivin), tumor suppressor proteins (Rb and p53), and some mediators involved in anoikis resistance and invasiveness (E-cadherin, N-cadherin, Twist, PTPN13 and SLUG) were evaluated.

Results: HPV genome was identified in 36.1% cases and 15.9% control samples, additionally there was found to be a statistic significant association between the presence of HPV and PCa (OR = 1.64, 95% C.I = 0.8-1.8, P-value = 0.023). HPV genotype 16 and 18 were the most prevalent genotype in both in the PCa group and the control group. The expression level of the tumor suppressor proteins (Rb and p53) and anti-apoptotic mediators (Bcl-2 and Survivin) were significantly decreased and increased, respectively, in the HPV-positive specimens compared to the HPV-negative specimens. Furthermore, the mean expression level of N-cadherin, SLUG, and TWIST in the HPV-positive specimens was higher than HPV-negative specimens while the mean expression level of PTPN-13 and E-cadherin genes in the HPV-positive specimens was lower than HPV-negative specimens.

Conclusion: Our study suggests that HPV infection may be involved in the development of PCa metastases by modulating anoikis resistance related genes.
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http://dx.doi.org/10.1016/j.micpath.2020.104576DOI Listing
March 2021

Assessment of oncogenic role of intestinal microbiota in colorectal cancer patients.

J Gastrointest Cancer 2020 Oct 3. Epub 2020 Oct 3.

Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

Introduction: The direct association between some microbial species and cancers, such as in colorectal cancer (CRC), has been disclosed.

Objective: The aim of this study was to evaluate the changes in intestinal microbiota in subjects with CRC compared with healthy group.

Methods: Three-hundred fecal specimens were gathered from patients with CRC and 300 from healthy individuals during March 2014 to October 2019 from two hospitals in Tehran. The informed consent form and the questionnaire were completed by the patients. Following the identification of Lactobaccilus acidophilus (L. acidophilus), Lactobacillus palntarom (L. palntarom), and Enterococcus faecalis (E. faecalis), the number of bacteria was determined using quantitative real-time PCR (qPCR).

Results: The patients' age range was 20-76 years (mean: 55.34 ± 3.66). The qPCR clarified that number of E. faecalis was 2.2-fold higher in patients with CRC compared to healthy population (p = 0.0013). Additionally, the number of L. acidophilus and L. plantarom was 3.4-fold (p < 0.0001) and 4.8-fold (p < 0.0001) higher in healthy population.

Conclusion: The inhibitory effect of intestinal microflora against the CRC development was proposed by observation of the changes in intestinal microbiota and determining their composition in subjects with CRC compared with that of healthy individuals. Microbiota was considered as a goal for the prevention and treatment of CRC. The relationship between microbiota and human health would be known deeper; this knowledge provides insights into the management of intestinal microbiota and therapeutics.
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http://dx.doi.org/10.1007/s12029-020-00531-8DOI Listing
October 2020

EBST: An Evolutionary Multi-Objective Optimization Based Tool for Discovering Potential Biomarkers in Ovarian Cancer.

IEEE/ACM Trans Comput Biol Bioinform 2020 May 7;PP. Epub 2020 May 7.

Ovarian cancer is the deadliest gynecologic malignancy, mainly due to limitations in early diagnosis. With advances in high-throughput technologies, research interest in identifying novel and customized tumor biomarkers for early detection and diagnosis is rapidly growing. Here we introduce a new tool called EBST to select microRNAs with biomarker potency in ovarian cancer. This tool has pre-processing options and Its core is the use of Modified Multi Objective Imperialist Competitive Algorithm and six objective functions based on the classifier performance/structure evaluation, clustering error and mRMR filter. In this paper, we used the FDR filter in the pre-processing stage and considered five objective functions, four of which relate to the l1-SVM classifier performance and one to the average mRMR ranking. The proposed method has identified 11 microRNAs including hsa-miR-6784-5p, hsa-miR-1228-5p, hsa-miR-8073, hsa-miR-6756-5p, hsa-miR-1307-3p, hsa-miR-4697-5p, hsa-miR-3663-3p, hsa-miR-328-5p, hsa-miR-1228-3p, hsa-miR-6821-5p, hsa-miR-1268a. Data classification by the proposed model showed 100% sensitivity, 99.38% specificity, 99.69% accuracy and 99.39% positive predictive value. In comparison with routine state-of-the-art methods, superiority of our method was confirmed. The biological evaluation of selected microRNAs using bioinformatics tools and published articles confirms their role in cancer signaling pathways. The tool and its MATLAB code are freely available at https://github.com/hanif-y.
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http://dx.doi.org/10.1109/TCBB.2020.2993150DOI Listing
May 2020