miR-381 Reverses Multidrug Resistance by Negative Regulation of the Pathway in HepG2/Dox Cells, and the Diagnostic and Prognostic Values of / Are Identified in Patients with LIHC.

Multidrug resistance (MDR) is the biggest challenge in cancer therapy. In this study, we explored the molecular mechanism of MDR in human liver cancer and explored the related diagnostic and prognostic values of the targeted genes in patients with hepatocellular carcinoma. We constructed a multidrug-resistant liver cancer cell line, HepG2/Dox, using the parental subline HepG2. The (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay was used to test the viability of the liver cancer cells. Western blotting was performed to test the expression of , β-catenin, and β-actin. Luciferase assays were performed to confirm the relationship between miR-381 and its target genes. The diagnostic and prognostic values of target genes were analyzed using publicly available data from The Cancer Genome Atlas. The Mann-Whitney test and logistic regression were performed to evaluate the association between or expression and clinical features in patients with liver hepatocellular carcinoma (LIHC). Finally, Kaplan-Meier and Cox regression analyses were performed to test the effect of or expression on the overall survival of patients with LIHC. expression was upregulated in HepG2/Dox cells. was found to be a direct target of hsa-miR-381 and was negatively regulated by has-miR-381. Moreover, hsa-miR-381 directly targeted the 3' UTR and decreased the luciferase activity of . Transfection with miR-183 partially reversed chemotherapeutic drug resistance by downregulating the expression of and in HepG2/Dox cells. Spearman's analysis results showed that and were positively correlated in patients with liver cancer, and increased and expression occurred in patients with liver cancer. High expression of and indicated poor prognosis in patients with liver cancer; however, neither nor expression was an independent diagnostic factor in patients with LIHC. Overexpression of hsa-miR-381 partially reversed the MDR of HepG2 cells by directly targeting and negatively regulating the expression of CTTNB1 and . Moreover, high expression of or indicated poor prognosis in patients with liver cancer.