Carcinogenesis Advance Access published online on August 18, 2008
Carcinogenesis, doi:10.1093/carcin/bgn195
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma
1 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences
2 State Key Laboratory of Oncology in Southern China
3 Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou 510275, P.R. China
* To whom correspondence should be addressed: S-M Zhuang, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Xin Gang Xi Road 135, Guangzhou 510275, P. R. China. Tel: 20-84112164; Fax: 20-84112169; E-mail: zhuangshimei{at}163.com, LSSZSM{at}mail.sysu.edu.cn
A G>C polymorphism (rs2910164) is located in the stem region opposite to the mature miR-146a sequence, which results in a change from G:U pair to C:U mismatch in the stem structure of miR-146a precursor. Here, we elucidated the biological significance of this polymorphism, based on cancer association study and cell model system. The cancer association study included 479 hepatocellular carcinoma (HCC) and 504 control subjects. We found that the genotype distribution of this polymorphism in HCC cases was significantly different from that in control subjects (P = 0.026). The association between the genotype and the risk of HCC was further analyzed using multivariate unconditional logistic regression, with adjustment for sex, age and HBV status. The results revealed that male individuals with GG genotype were two-fold more susceptible to HCC (OR = 2.016, 95% CI = 1.056-3.848, P = 0.034) compared to those with CC genotype. We next examined the influence of this polymorphism on the production of mature miR-146a and found that G-allelic miR-146a precursor displayed increased production of mature miR-146a compared with C-allelic one. Further investigations disclosed that miR-146a could obviously promote cell proliferation and colony formation in NIH/3T3, an immortalized but non-transformed cell line. These data suggest that the G>C polymorphism in miR-146a precursor may result in important phenotypic traits that have biomedical implications. Our findings warrant further investigations on the relation between miRNA polymorphism and human diseases.
Received June 20, 2008; revised July 27, 2008; accepted August 7, 2008.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T Paranjape, F J Slack, and J B Weidhaas MicroRNAs: tools for cancer diagnostics Gut, November 1, 2009; 58(11): 1546 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sun, J. Yan, K. Noltner, J. Feng, H. Li, D. A. Sarkis, S. S. Sommer, and J. J. Rossi SNPs in human miRNA genes affect biogenesis and function RNA, September 1, 2009; 15(9): 1640 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, H. Huang, L. Sun, M. Yang, C. Pan, W. Chen, D. Wu, Z. Lin, C. Zeng, Y. Yao, et al. MiR-21 Indicates Poor Prognosis in Tongue Squamous Cell Carcinomas as an Apoptosis Inhibitor Clin. Cancer Res., June 15, 2009; 15(12): 3998 - 4008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fabbri, N. Valeri, and G. A. Calin MicroRNAs and genomic variations: from Proteus tricks to Prometheus gift Carcinogenesis, June 1, 2009; 30(6): 912 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Su, J.-R. Yang, T. Xu, J. Huang, L. Xu, Y. Yuan, and S.-M. Zhuang MicroRNA-101, Down-regulated in Hepatocellular Carcinoma, Promotes Apoptosis and Suppresses Tumorigenicity Cancer Res., February 1, 2009; 69(3): 1135 - 1142. [Abstract] [Full Text] [PDF]
|
|