Abstract:

MicroRNAs (miRNAs) are small, non-coding RNAs that can act as oncogenes or tumor suppressors in human cancer. Recently we identified 129 known miRNA genes in the recurrent chromosomal aberration regions of hepatocellular carcinoma (HCC). Further analysis showed that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is often expressed together with its host gene FAK, and significantly increases HCC cell migration and invasion in vitro and in vivo by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, we analyzed the miRNA profiles in HCC and found that 69 miRNAs were differentially expressed between HCC and corresponding noncancerous liver tissues. The set of differentially expressed miRNAs could distinctly classify HCC and noncancerous liver tissues. Moreover, some of these differentially expressed miRNAs were related to the clinical features of HCC patients such as metastasis and recurrence. Importantly, the expression level of individual miRNA miR-125b was correlated with the survival time of HCC patients. These results revealed the diagnostic and prognostic implications of miRNAs in HCC. Furthermore, we showed that miR-125b could function as a candidate tumor suppressor in HCC through directly targeting oncogene LIN28B, thus resulting in the increase of p21Cip1/Waf1 expression and cell cycle arrest at G1/S transition. Moreover, we analyzed the function and mechanism of metastasis-related miR-30d in HCC and found that miR-30d could promote HCC cell migration and invasion by downregulating Galphai2 (GNAI2) expression. Intriguingly, we found that miRNA can target the coding region of mRNA other than its 3’ UTR; and experimentally showed that one mRNA could be simultaneously regulated by multiple miRNAs.

Key words: MicroRNA, hepatocellular carcinoma, miR-151, miR-125b, miR-30d