Abstract
BackgroundMicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach.MethodsAn updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association.ResultsOverall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC) while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096–1.481, P = 0.002). Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.ConclusionsThe present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.
Highlights
MicroRNAs are a class of endogenous, small nonprotein-coding single-stranded RNA molecules of,22 nucleotides in length that regulate a broad range of biologic and pathologic processes [1,2]
Mature miRNAs regulate the expression of approximately 30% of all human genes involved in fundamental biological processes at post-transcriptional level by sequence-specific binding to 39 untranslated regions (UTRs) of multiple target messenger RNAs, leading to their degradation or translational suppression [3]
Inclusion and Exclusion Criteria All miRNA association studies were included in the present meta-analysis if they met the following criteria: 1) case-control study, 2) outcome cancer, and 3) sufficient data for examining an odds ratio (OR) with 95% confidence interval
Summary
MicroRNAs (miRNAs) are a class of endogenous, small nonprotein-coding single-stranded RNA molecules of ,22 nucleotides in length that regulate a broad range of biologic and pathologic processes [1,2]. Mature miRNAs regulate the expression of approximately 30% of all human genes involved in fundamental biological processes at post-transcriptional level by sequence-specific binding to 39 untranslated regions (UTRs) of multiple target messenger RNAs (mRNAs), leading to their degradation or translational suppression [3]. Recent studies have implicated miRNAs in the genesis, progression (proliferation, migration and invasion) and prognosis of multiple human malignancies [4], including their key role in promoting cancer stem cell tumorigenicity [5]. Variations in miRNA expression may promote carcinogenesis by modulating the expression patterns of essential genes involved in tumor growth and progression [10]. Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach
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