LncRNA HOTAIR contributes Taxol-resistance of hepatocellular carcinoma cells via activating AKT phosphorylation by down-regulating miR-34a
Yunfei Duan, Jing Chen, Yang Yu, Zhen Qu, Yunjie Lu, Donglin Sun
Abstract
Drug resistance of Taxol leads to the treatment failure in hepatocellular carcinoma (HCC). LncRNA HOTAIR have drawn increasing attention in various diseases; its function and mechanism in Taxol-resistance in HCC remain unclear. In the present study, the two Taxol resistant HCC cell lines (HepG2/Taxol and SMMC7721/Taxol) were induced. The qRT-PCR data exhibited that over-expressed HOTAIR as well as low-expressed miR-34a were founded in HepG2/Taxol and SMMC7721/Taxol cells. HOTAIR knockdown suppresses proliferation, invasion and promotes apoptosis of in HepG2/Taxol and SMMC7721/Taxol cells through up-regulating miR-34a by MTT assay, transwell invasion assays and flow cytometry, while down-regulation of miR-34a had an opposite effect on reversing Taxol resistance. Cleaved caspase-3 and Bax were significantly up-regulated by si-HOTAIR transfection, while Bcl-2 level exhibited opposite trend. Besides, HOTAIR knockdown impaired Taxol-resistance in HCC by accommodating Akt phosphorylation and Wnt/β-catenin signaling via interacting with miR-34a. The present study may afford a valuable target for treating Taxol-resistance in HCC.