Abstract
BackgroundMicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. Recent studies investigating the association between hsa-mir-499 polymorphism (rs3746444) and cancer risk have yielded conflicting results.MethodsIn this meta-analysis, we conducted a search of case–control studies on the associations of SNP rs3746444 with susceptibility to cancer in electronic databases. A total of 31 studies involving 12799 cases and 14507 controls were retrieved and the strength of the association was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in controls. Subgroup analyses were done by racial descent and cancer type. Publication bias of literatures was evaluated by visual inspection of funnel plots and the linear regression asymmetry test by Egger et al. Sensitivity analysis was conducted by excluding one study at a time to examine the influence of individual data set on the pooled ORs.ResultsOverall, significant association between rs3746444 polymorphism and susceptibility to cancer was identified in TC versus TT and TC/CC versus TT (dominant) models. In the stratified analyses, increased risks were found in Asians, but not in Caucasians in all comparison models tested. Moreover, significant association with an increased risk was found in Chinese population. Also, much higher significant association with increased cancer risks were found in Iranian population. In different cancer types, a decreased risk was found in esophageal cancer.ConclusionOur meta-analysis suggested that hsa-mir-499 rs3746444 T > C polymorphism is associated with the risk of cancer in Asians, mainly in Iranian and Chinese population. However, rs3746444 T > C polymorphism is negatively associated with the risk of esophageal cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0126-1) contains supplementary material, which is available to authorized users.
Highlights
MicroRNAs are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target messenger RNA (mRNA), and are involved in diverse biological and pathological processes
In summary, though with limitations, our meta-analysis suggested that hsa-mir-499 rs3746444 T > C polymorphism is associated with the risk of cancer, especially in Asians, mainly in Chinese and Iranians
Rs3746444 T > C polymorphism is negatively associated with the risk of esophageal cancer
Summary
MicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. MiRNAs are hairpin-derived RNAs ~20-24 nucleotides long, which post-transcriptionally repress the expression of target genes usually by binding to the 3′-untranslated region (3′ UTR) of messenger RNA (mRNA) in a broad range of organisms in both normal physiological and disease contexts [11,12]. The resulting transcripts adopt a stem-loop structure and are exported to the cytoplasm where they are subsequently processed by another RNase III (Dicer) to generate mature double-stranded ~22 nt miRNAs [15]. One strand of this duplex is incorporated into an Argonautecontaining RNA-induced silencing complex (RISC), resulting in the translational repression and/or degradation of their target mRNAs [16]
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