Downregulation of long noncoding RNA CRNDE suppresses drug resistance of liver cancer cells by increasing microRNA-33a expression and decreasing HMGA2 expression.

At present, some researches have revealed the participation of long noncoding RNAs (lncRNAs) in liver cancer, but few of them have mentioned the role of CRNDE in drug resistance of liver cancer. Hence, this study is conducted to understand the role of CRNDE on liver cancer by regulating microRNA-33a (miR-33a) and high mobility group protein A2 (HMGA2) in liver cancer. First, drug-resistance model (HepG2 and BEL-7402) of human liver cancer cells was established. Then, CRNDE expression in drug-resistant cell lines (HepG2/adriamycin [ADM], BEL-7402/ADM) and parental cell lines (HepG2, BEL-7402) was detected. Furthermore, HepG2/ADM and BEL-7402/ADM cell lines with poor CRNDE expression or miR-33a overexpression was constructed. Next, drug-resistance index was calculated, and cell proliferation, apoptosis, migration, and invasion were detected, respectively. Then, the growth of tumor was observed in nude mice. Finally, the binding relationship between CRNDE and miR-33a and the targeting relationship between miR-33a and HMGA2 were verified. LncRNA CRNDE expressed highly in drug-resistant cells of liver cancer. Downregulated CRNDE and upregulated miR-33a-inhibited cells drug-resistance and promoted their apoptosis in liver cancer drug-resistant cells. CRNDE adsorbing and inhibiting miR-33a to promote HMGA2 in liver cancer drug-resistant cells by acting as a ceRNA. Silencing CRNDE or up-regulating miR-33a inhibited tumor growth of liver cancer in vivo. Our study provides evidence that downregulated CRNDE could upregulate miR-33a and inhibit HMGA2 expression, thus significantly promotes apoptosis of liver cancer cells and inhibiting its proliferation, migration, invasion and drug resistance.