Inhibition of proliferation and invasion of hepatocellular carcinoma cells by lncRNA-ASLNC02525 silencing and the mechanism

One of the most differentially expressed long non-coding RNAs (lncRNAs) that we identified by high throughput screening from liver cancer and para-carcinoma tissues, ASLNC02525, was highly expressed in the tissues and cell lines of liver cancer but not in adjacent tissues or normal hepatic cells. Knockdown of ASLNC02525 in hepatocellular carcinoma cells inhibited the proliferation and invasion. In the process, expression level of transcription factor twist1 (twistrelated protein 1) was reduced, but no change at transcription level was observed. According to bioinformatics analysis, ASLNC02525 may play a crucial role in inactivation of regulation of twist1 by hsa-miRNA-489-3p. The mechanism study revealed that ASLNC02525, as an RNA sponge, broke the negative regulation of twist1 by hsa-miRNA-489-3p, and once ASLNC02525 was silenced, the highly expressed hsa-miRNA489-3p regained its regulation on twist1 and inhibited the proliferation and invasion. The importance of this study lies in shedding light on the potential for lncRNAs to become targets for gene therapy, by demonstrating that lncRNAs can suppress tumor inhibiting activity of miRNAs via breaking regulation of some miRNA target genes.