Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21
- 1.1k Downloads
Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers. Although lncRNA GAS5 (growth arrest-specific transcript 5) has been characterized as a tumor suppressor in some kinds of cancer, its role and function in hepatocellular carcinoma (HCC) remain unknown. The present report demonstrates that there are lower levels of GAS5, PDCD4, and PTEN and higher levels of microRNA-21 (miR-21) in HCC tissues than in adjacent normal tissues. Moreover, the levels of GAS5 and miR-21 were correlated with the clinicopathological characteristics of HCC. HCC patients with higher levels of GAS5 or with the lower levels of miR-21 have longer survival times. There are lower levels of GAS5 and higher levels of miR-21 in HCC cell lines (Be7402, SMMC-7721, and HCCLM3) than in normal liver L-02 cells, and the levels correlate with the aggression of the HCC cell lines. Knockdown of GAS5 upregulates miR-21 levels in Bel-7402 cells (weakly aggressive); in contrast, there are opposite changes in HCCLM3 cells (highly aggressive). Moreover, GAS5 that upregulated or downregulated the expression of PDCD4 and PTEN was reversed by inhibiting or overexpressing miR-21 level in Bel-7402 and HCCLM3 cells. Then, overexpression of GAS5 suppresses the migration and invasion of HCC cells and high expression of miR-21 largely eliminates GAS5-mediated suppression of HCC cell migration and invasion. Thus, GAS5 acts as a tumor suppressor in HCCs through negative regulation of miR-21 and its targets and proteins about migration and invasion in cancer cells, which may be a target for treating HCC.
KeywordsHepatocellular carcinoma lncRNA GAS5 miR-21 Migration and invasion
The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA) for editing. This work was supported by the Natural Science Foundations of China (81272713, 81273114, and 81100253), Natural Science Foundations of Jiangsu Province (BK20131437), and by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (2010).
Conflicts of interest
- 11.Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP: Noncoding RNA GAS5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal 2010;3:ra8.Google Scholar
- 12.Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, Song Y: A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Molecular carcinogenesis 2013Google Scholar
- 34.Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 1832;2013:1613–23.Google Scholar