MicroRNAs (miRNAs) are noncoding RNAs that function as post-transcriptional regulators of tumor oncogenes and suppressors. Single-nucleotide polymorphisms (SNPs) in miRNA genes are a novel class of genetic variations in the human genome that are currently being identified and investigated in human cancers. In this study, we aimed to investigate whether SNPs in the miR-27a gene affect miR-27a expression and alter susceptibility to gastric cancer. Therefore, we conducted a case-control population study and the allele and genotype frequencies for polymorphism rs11671784 in miR-27a gene were examined in the study population. As a result, we found that the G/A polymorphism in the miR-27a gene exhibited a significant effect on gastric cancer risk. Compared with GG homozygotes, subjects who were GA heterozygotes or AA homozygotes exhibited a decreased risk of gastric cancer. The G/A polymorphism impaired the processing of pre-miR-27a to mature miR-27a, resulting in significantly reduced expression of mature miR-27a and an increased level of its target HOXA10. Furthermore, we confirmed these findings in in vitro studies by overexpressing pre-miR-27a carrying G or A allele. It provided further evidence demonstrating that allelic difference of rs11671784 is linked to gastric tumorigenesis. In summary, our results indicate that the G/A polymorphism in miR-27a gene (rs11671784) decreases miR-27a expression, reduces gastric cancer risk and plays a role in gastric tumorigenesis. This is the first study to address the role and function of miR-27a polymorphism rs11671784 in gastric cancer. These results could be useful to assess individual susceptibility of gastric cancer and will improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.

BackgroundOur recent study showed the global physiological function of the differentially expressed genes of prostate cancer in Chinese patients was different from that of other non-Chinese populations. microRNA are estimated to regulate the expression of greater than 60% of all protein-coding genes. To further investigate the global association between the transcript abundance of miRNAs and their target mRNAs in Chinese patients, we used microRNA microarray approach combined with bioinformatics and clinical-pathological assay to investigate the miRNA profile and evaluate the potential of miRNAs as diagnostic and prognostic markers in Chinese patients.ResultsA total of 28 miRNAs (fold change ≥1.5; P ≤ 0.05) were differentially expressed between tumor tissue and adjacent benign tissue of 4 prostate cancer patients.10 top Differentially expressed miRNAs were validated by qRT-PCR using all 20 tissue pairs. Compared to the miRNA profile of non-Chinese populations, the current study showed that miR-23b, miR-220, miR-221, miR-222, and miR-205 maybe common critical therapeutic targets in different populations. The integrated analysis for mRNA microarray and miRNA microarray showed the effects of specifically inhibiting and/or enhancing the function of miRNAs on the gene transcription level. The current studies also identified 15 specific expressed miRNAs in Chinese patients. The clinical feature statistics revealed that miR-374b and miR-19a have significant correlations with clinical-pathological features in Chinese patients.ConclusionsOur findings showed Chinese prostate cancer patients have a common and specific miRNA expression profile compared with non-Chinese populations. The miR-374b is down-regulated in prostate cancer tissue, and it can be identified as an independent predictor of biochemical recurrence-free survival.

The aim of the current study was to explore the possible association of the polymorphism of C(-735)T in MMP-2 with the vulnerable plaque risk in ultrasound-confirmed carotid atherosclerosis cases. Serum MMP-2 levels were measured to investigate the relationship between the MMP-2 level and the genetic variability. The MMP-2 polymorphism was detected by PCR-RFLP in the 243 cases with stable plaque and 221 cases with vulnerable plaque. Serum MMP-2 levels were measured with ELISA. The results showed that MMP-2 was significantly higher in the cases with vulnerable plaque than in the cases with stable plaque. A statistical difference was found between the genotype distributions in the vulnerable plaque cases and that in the stable cases. T-allele frequency was also found to be over-represented in the stable plaque cases than in the vulnerable plaque cases, which might partially explain the observed difference in the serum MMP-2 levels in the different plaque cases. The current results also suggested that MMP-2 was a risk factor in the cases with vulnerable plaques, whereas TT genotype and T allele might be protective factors in the cases with vulnerable plaques.

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