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Genetic variations in miR-27a gene decrease mature miR-27a level and reduce gastric cancer susceptibility

Oncogene volume 33, pages 193–202 (2014)Cite this article

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Abstract

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.

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Acknowledgements

We thank Xin Zhou and Wei Li (Department of General Surgery, First Affiliated Hospital of Nanchang University) for collecting the clinicopathologic information utilized in this study. We thank Chengjie Liang (Laboratory Animal Center, Guangzhou Medical University) for assistance with the nude mice assays. This work was supported by the National Natural Science Foundation of China (30771780, 30972443 to YJ and 81102099 to QY), the Natural Science Foundation of Guangdong Province (9251018201000004 to YJ), the University Talent Program of Guangdong (2010-79 to YJ) and the University Talent Program of Guangzhou (10A003D to YJ).

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Authors and Affiliations

  1. Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, People’s Republic of China

    Q Yang, Z Han, J Wu & Y Jiang

  2. Department of General Surgery, First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China

    Z Jie & Z Li

  3. Department of Medical Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

    S Ye

  4. Department of Physiology and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA

    C Yang

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  1. Q Yang
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Correspondence to Y Jiang.

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Yang, Q., Jie, Z., Ye, S. et al. Genetic variations in miR-27a gene decrease mature miR-27a level and reduce gastric cancer susceptibility. Oncogene 33, 193–202 (2014). https://doi.org/10.1038/onc.2012.569

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