hsa-miR-146a

hepatocellular carcinoma (HCC)

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

up-regulated

Validated targets of miRNA from the reference:

unknown

Validated targets of miRNA from TarBase:

unknown : More...

Description:

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 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.

Reference:

A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. | PMID:18711148
Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM.
Carcinogenesis. 2008 Aug 18. [Epub ahead of print]