Background: Esophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are acknowledged; however, genetic... more
Background: Esophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are acknowledged; however, genetic defects can significantly contribute to predisposition to GIT cancers. Accordingly, recent works have shown that single-nucleotide polymorphisms (SNPs) within miRNAs coding sequence (miR-SNPs) and miRNA target sites (target-SNPs) may further contribute to increased risk of developing cancer. Objectives: In this study, we comprehensively identified miRNA-target gene pairs implicated in GIT cancers and catalogued the presence of potentially functional miR-SNPs and target-SNPs that impair the correct functional recognition. Materials and Methods: Using bioinformatics tools, manual literature review, and a highly accurate dataset of experimentally validated miRNA-target gene interactions, we compiled a list of miRNA-target genes pairs related to GIT cancers and prioritized them into different groups based on the levels of experimental support. Functional annotations (gene ontology) were applied to these pairs in each group to gain further information. Results: We identified 97 pairs in which both miRNAs and target genes were implicated in GIT cancers. Several pairs, denoted as highly polymorphic pairs, had both miR-SNPs and target-SNPs. In addition, more than 5000 miRNA-target gene pairs were identified in which, according to the previous reports, either the miRNAs or the target genes had a direct involvement in GIT cancers. More than 800 targetSNPs are located in regulatory regions that were extracted from the ENCODE project through the RegulomeDB database. Of these, 20 were classified as expression quantitative trait loci (eQTLs). Conclusions: Our work provided a comprehensive source of prioritized and annotated candidate polymorphisms inside miRNAs and their target sites in GIT cancers, which would facilitate the process of choosing right candidate miRNA-target genes and related polymorphisms for future association or functional studies. Keywords:MicroRNAs; Gastrointestinal Neoplasms; Colorectal Neoplasms; Gastric Neoplasms; Esophageal Neoplasms; Single Nucleotide Polymorphisms
Childhood Hepatitis B virus (HBV) infection causes both medical and public health challenges. Infants who acquire HBV parentally have up to 90% risk of developing chronic HBV infection. It is now estimated that approximately 10% of... more
Childhood Hepatitis B virus (HBV) infection causes both medical and public health challenges. Infants who acquire HBV parentally have up to 90% risk of developing chronic HBV infection. It is now estimated that approximately 10% of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. In this distribution, elevated rate and prevalence of HBV marker have been found in patients with malignancies as compared to the general population. By reviewing the web-based search for all Persian and English types of scientific peer review published articles initiated using Iran Medex, MEDLINE/PubMed, CINAHL and other pertinent references on websites about HBV and HCV blood disorders. The high prevalence of HBV and HCV infective markers was detected in patients with different malignancies. Moreover, identification of high prevalence of HBV infective markers in leukemia patients proposed strong association between hepatitis viral infections and leukemia.
The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of... more
The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies.
AIMS: Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an individual's susceptibility to coronary artery disease (CAD). In the present study, the association between... more
AIMS: Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an individual's susceptibility to coronary artery disease (CAD). In the present study, the association between two such SNPs (rs2910164 in miR-146a and rs12190287, which disrupts miRNA binding to TCF21) and CAD, in an Iranian population, was evaluated and in silico analyses were conducted to predict disease-related effects of miR-146a rs2910164. METHODS: The study population consisted of angiographically confirmed CAD patients (n = 300) and asymptomatic controls (n = 300). Genotyping was performed using the TaqMan genotyping assay. RESULTS: A multivariate regression analysis revealed that rs2910164 was associated with an increased CAD risk in the dominant model. In comparison to GG homozygotes, individuals who carry at least one C allele had a significantly higher risk of CAD (GC+CC vs. GG, odds ratios [OR]: 1.82, 95% confidence intervals [CI]: 1.18-2.80, p = 6.358e-3). Similarly, TCF21 rs12190287 was observed to be associated with CAD in a log-additive model (OR: 0.63, 95% CI: 0.45-0.88, p = 6.584e-3). An in silico analysis revealed that rs2910164 may modify the miR-146a-3p-mediated regulation of several biological processes that are implicated in CAD, like those that are related to the regulation of apoptosis and immune response. CONCLUSIONS: Our data provide the first evidence for the association of miR-146a rs2910164 and TCF21 rs12190287 with CAD in an Iranian population, encouraging further research to elucidate the disease-related effects of miR-146a rs2910164.
In recent years, genome-wide association studies (GWAS) have made great progress in elucidating the genetic influence on complex traits. An overwhelming number of GWAS signals resides in regulatory elements, therefore most post-GWAS... more
In recent years, genome-wide association studies (GWAS) have made great progress in elucidating the genetic influence on complex traits. An overwhelming number of GWAS signals resides in regulatory elements, therefore most post-GWAS studies focused only on transcriptional regulatory variants. However, recent findings have expanded the spectrum of trait/disease-associated regulatory variants beyond transcriptional level and highlighted the importance of post-transcriptional variants like those in miRNA targetome. The present work integrated genome-wide association data of coronary artery disease (CAD) with population-specific linkage disequilibrium structures from 1000 Genomes Project to map disease associations to miRNA targetome. Moreover, we performed a variety of functional prediction analyses to prioritize disease-associated variants (DAVs) influencing miRNA targetome and in-silico analyses to get insights into their functional significance. In conclusion, although the role of miRNA targetome variations in the development of CAD still has to be fully elucidated, we provided a systematic bioinformatics approach to the miRNA targetome variations in CAD. The results of this study will be valuable for researchers interested in the identification of CAD GWAS signals that may implicate polymorphic miRNA targeting.
The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related... more
The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.
Background: miRNA-221 and miRNA-222 are two homologous microRNAs, the high-expression levels of which have been commonly demonstrated in the most current human cancer types as well as breast cancer. The purpose of this research was to... more
Background: miRNA-221 and miRNA-222 are two homologous microRNAs, the high-expression levels of which have been commonly demonstrated in the most current human cancer types as well as breast cancer. The purpose of this research was to determine the clinical value of measuring the expression level of hsa-miR-221-3p in breast cancer tissues and evaluate its biological and prognostic importance in breast cancer (BC).
Methods: A total of 40 tumor samples and matched tumor-free margin specimens were obtained during surgery from patients with BC. After total RNA extraction and cDNA synthesis, the relative expression level of hsa-miR-221-3p in tumor and marginal tissues was examined by quantitative real-time PCR. Moreover, the association between hsa-miR-221-3p expression and clinicopathological features of patients was detected.
Results: The relative expression level of hsa-miR-221-3p in BC tissues was significantly higher than that in adjacent noncancerous breast biopsies (p ≤ 0.0001). Also, there was no significant association between hsa-miR-221-3p expression with clinicopathological characteristics (p > 0.05). The receiver operating characteristic (ROC) curve analyses also represented an optimum cutoff point of < 4.34 to show that hsa-miR-221-3p is an effective molecular biomarker for BC diagnosis.
Conclusions: This study illustrated that analysis of hsa-miR-221-3p relative gene expression may be applied as a biomarker for screening BC patients and could be a substantial tool in diagnosis and prognosis. Also, that could be advantageous in decreasing surgical mistakes in tumor elimination through the surgery and enhancing all over the progression of surgery with reformed tumor clearance.
MicroRNAs are small non-coding RNAs of 18-25 nucleotides that regulate gene expression at the post-transcriptional level through binding to the 3´-UTR of mRNAs and block mRNA transcription or regulate its resistance. Increasing evidence... more
MicroRNAs are small non-coding RNAs of 18-25 nucleotides that regulate gene expression at the post-transcriptional level through binding to the 3´-UTR of mRNAs and block mRNA transcription or regulate its resistance. Increasing evidence indicates that dysregulation of miRNA is a hallmark of cancer. The miRNAs have an essential role in the regulation of oncogenes or tumor suppressor genes in cell signaling pathways. MiR-221 and miR-222 are two homologous microRNAs, the high expression levels of which have been commonly demonstrated in multiple human cancer types. The miR-221/miR-222 functions have been verifed as oncogenes or tumor suppressors. Here, we reviewed the roles of miR-221/miR-222 in various kinds of cancer progression and development: controlling proliferative signaling pathways, avoiding cell deaths resulted from tumor suppressors, monitoring angiogenesis and even supporting epithelial-mesenchymal transition. We discussed that miR-221/miR-222 act as promising biomarkers for detection of human cancer types and suggested a new pathway for molecular targeted cancer therapy.
Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles... more
Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures.
