LncRNA CDKN2B-AS1 promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis

Abstract

Long non-coding RNAs (lncRNAs) show great potential as therapeutic targets in many diseases including hepatocellular carcinoma (HCC). Here, we aimed to investigate the clinical significance and function of lncRNA CDKN2B antisense RNA 1 (CDKN2B-AS1) in HCC. Here, we identified a novel oncogenic lncRNA CDKN2B-AS1, which was highly expressed in HCC and positively associated with large tumor size, microvascular invasion, high tumor grade, advanced tumor stage and reduced survival of HCC patients. CDKN2B-AS1 knockdown inhibited cell proliferation, migration and invasion, and induced G1 arrest and apoptosis of HCC cells in vitro, and CDKN2B-AS1 silencing suppressed tumor growth and metastasis of HCC in vivo. In accordance, CDKN2B-AS1 overexpression accelerated HCC cell growth and metastasis. Mechanistically, CDKN2B-AS1 promoted nucleosome assembly protein 1 like 1 (NAP1L1) expression by sponging let-7c-5p, thereby activated PI3K/AKT/mTOR signaling in HCC cells. Notably, NAP1L1 restoration abolished the effects of CDKN2B-AS1 silencing on HCC cell growth and metastasis. CDKN2B-AS1, an oncogenic lncRNA of HCC, promoted NAP1L1-mediated PI3K/AKT/mTOR signaling by acting as a molecular sponge of let-7c-5p. Our findings indicate that CDKN2B-AS1 may be a potential prognostic biomarker and a candidate target for HCC therapy.

Keywords: CDKN2B antisense RNA 1; Liver cancer; Long non-coding RNA; Nucleosome assembly protein 1 like 1; Tumor progression.