Long noncoding RNA NNT-AS1 promotes hepatocellular carcinoma progression and metastasis through miR-363/CDK6 axis
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Ye-Bin Lu1, Qin Jiang2, Man-Yi Yang3, Ji-Xiang Zhou4 and Qi Zhang4
1Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410013, China
2Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, 410013, China
3National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, 410013, China
4Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, 410013, China
Qi Zhang, email: email@example.com
Keywords: hepatocellular carcinoma, long non-coding RNA, NNT-AS1, miR-363, CDK6
Received: July 07, 2017 Accepted: August 17, 2017 Published: September 28, 2017
Long non-coding RNAs (lncRNAs) have been tested to act as important regulator in liver cancer genesis and progression. LncRNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) has been reported to participate in the tumorigenesis. However, the exact molecular mechanism of NNT-AS1 in hepatocellular carcinoma (HCC) is still unknown. In present study, our team identified the up-regulated expression of NNT-AS1 in HCC tissue and cell lines compared with adjacent noncancerous tissue and normal cells. Moreover, HCC patients with high NNT-AS1 levels had poor prognosis than that with low NNT-AS1 level (p=0.0089). In vitro, gain- and loss-of-function experiments revealed that enhanced NNT-AS1 expression promoted the proliferation ability and alleviated the cycle arrest and apoptosis, while NNT-AS1 knockdown suppressed the proliferation and induced G0/G1 phase arrest and apoptosis. In vivo, NNT-AS1 knockdown inhibited the HCC neoplastic tumor volume and weight. Bioinformatics analysis and luciferase reporter assay validated that miR-363 targeted NNT-AS1 and CDK6 3’-UTR. MiR-363 was down-regulated in HCC tissue and cells. NNT-AS1 competed with CDK6 for miR-363 binding and could increase CDK6 expression. In summary, our results suggest the oncogenic role of NNT-AS1 in HCC tumorigenesis through miR-363/CDK6 axis, providing a novel therapeutic target for human HCC.
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