Long non-coding RNA TUG 1 regulates the development of multidrug resistance in hepatocellular carcinoma via Pgp and MDR 1

Multidrug resistance (MDR) is a significant impediment to the treatment of hepatocellular carcinoma (HCC), which leds to increasing resistance to different drugs. Taurine up-regulated gene 1 (TUG1), a 7.1-kb long non-coding RNA (lncRNA), was found to be up-regulated in HCC and promoted cell growth and apoptosis. However, its clinical significance and potential role in MDR in HCC remain unclear. In the present study, we identified the mRNA levels of TUG1 in HCC tissues of adriamycin-resistant patients and two kinds of adriamycin-resistant cells SMMC-7721/ADM and HepG2/ADM by qRT-PCR. After knockdown or overexpression of TUG1, the anticancer drug resistance was assessed by testing the cytotoxicity of adriamycin and apoptosis rate utilized by CCK-8 assay and flow cytometry, respectively. The expression level of several genes related to apoptosis, PARP and Caspase-3, were also detected by western blotting. Furthermore, we investigated the expression levels of P-gp and MDR1 by qRTPCR and western blotting. TUG1 was upregulated in HCC tissues of adriamycin-resistant patients and adriamycinresistant cells. Moreover, SMMC-7721/ADM and HepG2/ADM cells transfected with TUG1 siRNA and treated with adriamycinled to the lower survival rate and the higher tumor cells apoptosis. While, TUG1 overexpression led to the resistance to apoptosis in SMMC-7721 and HepG2 cells transfected with pcDNA-TUG1 and treated with adriamycin. Furthermore, we found that TUG1 down-regulation inhibited the expression of P-gp and MDR1. Taken together, knockdown of lncRNA TUG1 in HCC can effectively suppress the development of MDR by targeting P-gp and MDR1, suggesting a promising therapeutic target for reversing MDR in HCC therapy.