Emerging evidence has suggested that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is upregulated in hepatocellular carcinoma (HCC) and is associated with cell invasion, migration, and growth. However, the potential modulation mechanism remains to be elucidated. MiR-33a-5p and cyclin-dependent kinase 6 (CDK6) also participate in the pathophysiology of HCC. This work aims to investigate the effect of CRNDE on HCC apoptosis, invasion, and migration and elucidate the role of miR-33a-5p and CDK6 therein. CRNDE and CDK6 were upregulated in HCC tissues and cells, while miR-33a-5p was downregulated. Inhibition of CRNDE suppressed the invasion, migration, and proliferation of HCC cells and enhanced apoptosis by modulating proteins associated with mitochondrial apoptosis (caspase 3, Bax, cytochrome-c, Bcl-2), which were the same as the function of miR-33a-5p overexpression. The dual-luciferase reporter assay demonstrated that miR-33a-5p was a target of CRNDE, and in turn, CRNDE inhibition enhanced the level of miR-33a-5p. CDK6 was also revealed as a target of miR-33a-5p, and both CRNDE inhibition and miR-33a-5p overexpression suppressed CDK6 expression and led to G0/G1 phase block in HCC cells. In vivo experiments using a mouse xenograft tumor model further verified the interaction between CRNDE and miR-33a-5p, showing that miR-33a-5p overexpression or CRNDE inhibition suppressed CDK6 expression and HCC tumorigenesis. Overall, the present work indicated that CRNDE plays an oncogenic function in HCC through regulating the miR-33a-5p/CDK6 axis, revealing a potential therapeutic target in HCC.
Keywords: CDK6; CRNDE; Hepatocellular carcinoma; MiR-33a-5p; Targeted therapy.