Long non-coding RNAs (lncRNAs) have been identified as critical players in multiple cancers and lncRNAs are tightly linked to cancer progression. However, only little amount of lncRNAs have been identified to participate in the molecular mechanisms of the progression of hepatocellular carcinoma. In this study, we found that lncRNA-AK058003 is down-regulated in hepatocellular carcinoma tissues and it is associated with the relapse and metastasis of the cancer. Furthermore, lncRNA-AK058003 acts as a tumor suppressor, suppressing hepatocellular carcinoma cell proliferation and metastasis in vitro and in vivo. lncRNA-AK058003 can reduce mRNA stabilizing protein HuR, which results in the inhibition of the expression of γ-synuclein. In addition, a bioinformatics study indicated that γ-synuclein is a target of miR-15a. To verify whether lncRNA-AK058003 plays a role in miR-15a-mediated inhibition of γ-synuclein, we demonstrated that lncRNA-AK058003 is very likely to be a precursor of miR-15a. Collectively, lncRNA-AK058003 can reduce the expression of mRNA stabilizing protein HuR and act as a precursor of miR-15a to suppress γ-synuclein-mediated cell proliferation and the metastasis of hepatocellular carcinoma.
Keywords: liver cancer; lncRNA; mRNA stabilizing protein; tumor suppressor.