Differential expression of long non-coding RNAs (lncRNAs) plays critical roles in hepatocarcinogenesis. Considerable attention has focused on the antitumor effect of histone deacetylase inhibitor (Trichostatin A, TSA) as well as the coding gene expression-induced apoptosis of cancer cells. However, it is not known whether lncRNA has a role in TSA-induced apoptosis of human hepatocellular carcinoma (HCC) cells.
The global expression of lncRNAs and coding genes was analyzed with the Human LncRNA Array V2.0 after 24h treatment. Expression was verified in cell lines and tissues by quantitative real-time PCR. The data showed that 4.8% (959) of lncRNA and 6.1% (1849) of protein coding gene were significantly differentially expressed. The differential expressions of lncRNA and protein coding genes had distinguishable hierarchical clustering expression profiling pattern. Among these differentially expressed lncRNAs, the greatest change was noted for uc002mbe.2, which had more than 300 folds induction upon TSA treatment. TSA selectively induced uc002mbe.2 in four studied HCC cell lines. Compared with normal human hepatocytes and adjacent noncancerous tissues, uc002mbe.2 expression level was significantly lower in the HCC cell lines and liver cancer tissues. The TSA-induced uc002mbe.2 expression was positively correlated with the apoptotic effect of TSA in HCC cells. In addition, knockdown the expression of uc002mbe.2 significantly reduced TSA-induced apoptosis of Huh7cells. Therefore, TSA-induced apoptosis of HCC cells is uc002mbe.2 dependent and reduced expression of uc002mbe.2 may be associated with liver carcinogenesis.
- Yang H, Zhong Y, Xie H, Lai X, Xu M, Nie Y, Liu S, Wan YJ. (2013) Induction of the liver cancer-down-regulated long noncoding RNA uc002mbe.2 mediates trichostatin-induced apoptosis of liver cancer cells. Biochem Pharmacol [Epub ahead of print]. [abstract]