MicroRNA-591 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Lowering Drug Resistance through Inhibition of Far-Upstream Element-Binding Protein 2-Mediated Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Axis.

MicroRNAs, a group of noncoding regulatory RNAs, are involved in oncogenesis, cell survival, and chemosensitivity. First, microarray-based analysis predicted that far-upstream element-binding protein 2 (FBP2) was upregulated in hepatocellular carcinoma (HCC), which may be regulated by miR-591. In this study, we hypothesize an inhibitory role of miR-591 in HCC via regulating FBP2. Next, reverse transcription quantitative polymerase chain reaction found that FBP2 expressed highly and miR-591 expresses poorly in HCC tissues. Then, the negative correlation between miR-591 and mRNA expression of FBP2 was identified by Pearson's correlation coefficient, and putative miR-591-binding sites on the 3'-untranslated region of FBP2 was validated using a dual-luciferase reporter gene assay. After the expression of miR-591 and FBP2 was altered in the drug-resistant CD133+/CD44+ cells, a series of in vitro and in vivo experiments demonstrated that either miR-591 overexpression or FBP2 silencing inhibited the abilities of sphere formation and colony formation, drug resistance, as well as tumorigenicity. It was further observed that miR-591 could suppress FBP2 expression by blocking the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin axis. Above results highlighted an inhibitory effect of miR-591 on the development of HCC by reducing the drug resistance of HCC stem cells. It revealed miR-591 as a new target in the treatment of HCC.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}