Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression

作者：Sun, Qingmin^*; Gu, Haijuan; Zeng, Ying; Xia, Yi; Wang, You; Jing, Yali; Yang, Li; Wang, Bin

来源：CANCER SCIENCE, 2010, 101(10): 2241-2247.

DOI：10.1111/j.1349-7006.2010.01667.x

• TRANSCRIPTION FACTOR SP1
• ONCOGENIC MICRORNA-27A
• CHINESE POPULATION
• INCREASED RISK
• CELLS
• POLYMORPHISM
• SURVIVAL
• ASSOCIATION
• PROGRESSION
• SIGNATURE

Aberrant microRNA (miRNA) expression is presently proposed to correlate with various human cancers and common single-nucleotide polymorphisms (SNP) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. However, whether miRNAs SNP alter gastric cancer susceptibility is still unclear. Here we investigated the possible role of a common A/G polymorphism (rs895819) within hsa-mir-27a in the development or progression of gastric cancer, and assessed the effect of rs895819 on the expression of miR-27a and its target gene Zinc finger and BTB domain containing 10 (ZBTB10). In the present case-control study, we found that subjects with the variant genotypes (AG + GG) showed a significantly increased risk of gastric cancer relative to AA carriers (adjusted odds ratio = 1.48, 95% confidence interval 1.06-2.05; P = 0.019). The elevated risk was especially evident in older subjects (age > 58 years), men, nonsmokers and rural subjects. A significant association of hsa-mir-27a variant genotypes with lymph node metastasis was also observed. Further functional analyses indicated that variant genotypes might be responsible for elevated miR-27a levels and reduced ZBTB10 mRNA. Moreover, an inverse correlation was found between ZBTB10 and miR-27a levels. In conclusion, we were the first to show that a common polymorphism (rs895819) in hsa-mir-27a, by modulating miR-27a and ZBTB10 levels, acted as an important factor of the gastric cancer susceptibility. (Cancer Sci 2010).

• 出版日期2010-10
• 单位南通市肿瘤医院; 南京医科大学