Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one type of the most common malignant tumors, accounting for the second leading cause of worldwide cancer-related deaths with an increasing incidence annually [1, 2]
Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) was up-regulated in hepatocellular carcinoma (HCC) tissues and correlated with poor prognosis
In HCC, a growing number of Long non-coding RNAs (lncRNAs) have been reported to participate in the occurrence, progression and metastasis, for example MALAT1, MEG3 and UCA1 [17,18,19,20]
Summary
Hepatocellular carcinoma (HCC) is one type of the most common malignant tumors, accounting for the second leading cause of worldwide cancer-related deaths with an increasing incidence annually [1, 2]. The examination methods and therapeutic methods for HCC is upgrading, the overall survival rates of HCC patients are still very poor [3]. It has great challenge to investigate novel biomarkers and therapeutic targets for early detection of HCC [4]. With the development of high-throughput RNA sequencing and bioinformatics analysis, numerous newfound lncRNAs have been reported to act as oncogenes or tumor suppressors in multiple oncogenesis progression. LncRNA SNHG1 is remarkably upregulated in HCC tissues and cell lines, and promotes the HCC cell proliferation, invasion and migration through www.impactjournals.com/oncotarget
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