Abstract
Hepatocellular carcinoma (HCC) is a principal histologic type of liver cancer with high mortality. Long non-coding RNAs (LncRNAs) exert a crucial role in the pathogenesis of human tumors. To date, the functions and mechanisms of lncRNA HAGLROS in HCC are rarely reported. In the current study, HAGLROS exhibited a higher level in HCC tissues and cells. HAGLROS expression was positively correlated with tumor size, TNM stage and poor clinical prognosis. Loss-of-function experiments showed that knockdown of HAGLROS significantly lowered cell proliferation, cell cycle progression, migration, invasion and epithelial to mesenchymal transition (EMT) but induced apoptosis in vitro. Consistently, tumor growth in the nude mice was effectively slowed by the depletion of HAGLROS. Mechanistically, HAGLROS could competitively bind to miR-26b-5p to prevent the suppression of miR-26b-5p on its downstream target gene Karyopherin α2 (KPNA2). Moreover, the inhibitory effects of HAGLROS knockdown on cell malignant behaviors were reversed due to the miR-26b-5p down-regulation or KPNA2 overexpression. It was interesting to note that HAGLROS inactivated p53 signaling through targeting miR-26b-5p/KPNA2. In conclusion, our results demonstrated that HAGLROS contributed to the malignant progression of HCC via serving as a sponge for miR-26b-5p to facilitate KPNA2 expression and inactivate p53 signaling. Targeting HAGLROS/miR-26b-5p/KPNA2 axis might be an alternative therapeutic strategy for HCC patients.