ANT2 suppression by shRNA restores miR-636 expression, thereby downregulating Ras and inhibiting tumorigenesis of hepatocellular carcinoma.

ANT2 suppression by shRNA restores miR-636 expression, thereby downregulating Ras and inhibiting tumorigenesis of hepatocellular carcinoma. Exp Mol Med. 2013;45:e3 Authors: Jang JY, Lee YS, Jeon YK, Lee K, Jang JJ, Kim CW Abstract MicroRNAs (miRNAs) participate in diverse biological functions and carcinogenesis by inhibiting specific gene expression. We previously reported that suppression of adenine nucleotide translocase 2 (ANT2) by using the short hairpin RNA (shRNA) approach has an antitumor effect in several cancer cells. We here examined the influence of ANT2 on expression of miRNAs in hepatocellular carcinoma (HCC) to further elucidate the tumor-suppressive mechanism of ANT2 shRNA. We first carried out screening for miRNAs, whose expression is regulated by ANT2 suppression in the Hep3B HCC cell line using miRNA microarrays. Validation of candidate miRNAs was done by incorporating clinical samples, and their effects on the tumorigenesis of HCC were studied in vitro and in vivo. miR-636 was one of the miRNAs whose expression was highly upregulated by ANT2 suppression in miRNA microarray analysis, as confirmed by real-time reverse transcription-polymerase chain reaction. Notably, miR-636 was markedly downregulated in HCC tissues compared with matched non-neoplastic liver in clinical samples. Restoration of miR-636 in Hep3B cells led to significant reduction of cell proliferation and colony formation. miR-636 restoration resulted in a decre...
Source: exp Mol Med - Category: Molecular Biology Authors: Tags: Exp Mol Med Source Type: research