Long non-coding RNA AK058003, as a precursor of miR-15a, interacts with HuR to inhibit the expression of γ-synuclein in hepatocellular carcinoma cells.

Xiaoqin He,Huilin Liang,Yujie Zhou,Yuefeng Zhang,Wei Ge,Yuanyuan Gan,Junjian Deng,Ximing Xu,Dongcheng Wu,Yongfa Zheng

doi:10.18632/oncotarget.14276

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) has a poor prognosis and, after clinical diagnosis, is considered a deadly carcinoma that generally results in intra and extra hepatic metastasis
We found that Long non-coding RNAs (lncRNAs)-AK058003 is down-regulated in hepatocellular carcinoma tissues and it is associated with the relapse and metastasis of the cancer
LncRNAAK058003 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

Summary

Introduction

Hepatocellular carcinoma (HCC) has a poor prognosis and, after clinical diagnosis, is considered a deadly carcinoma that generally results in intra and extra hepatic metastasis. In spite of the improvement in prevention and treatment, HCC is still in the second leading cause of death worldwide [1]. Previous studies have reported many genes involved in HCC, the molecular mechanisms remain unclear. A better understanding of the pathophysiological mechanisms of HCC is critical for uncovering molecular markers and developing therapeutic strategies. The lncRNAs play an important role in the regulation of gene expression in normal physical conditions. The dysregulation of lncRNAs have been shown to be involved in the genesis, development and drug-resistance of many different cancers [3,4,5]

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