LncRNA TUG1 promotes cisplatin resistance in esophageal squamous cell carcinoma cells by regulating Nrf2

Abstract

AbstractEsophageal squamous cell carcinoma (ESCC) is a common malignancy with poor prognosis. The drug resistance compromises the efficacy of chemotherapy for ESCC. Long non-coding RNA taurine upregulated gene 1 (TUG1) has been identified as a promoter of cancer progression and chemotherapy resistance in many malignancies. However, the exact role of TUG1 in ESCC chemotherapy resistance remains unclear. In this study, we showed that TUG1 expression in TE-1-derived cisplatin (DDP)-resistant (TE-1/DDP) cells was higher than that in TE-1 cells. Furthermore, TUG1 promoted DDP resistance in TE-1 and TE-1/DDP cells by promoting cell proliferation, suppressing cell apoptosis, and elevating protein expression of the classical multi-drug resistance-related P-gp. In contrast, TUG1 knockdown exerted an opposite effect. Mechanistically, RNA pull-down and RNA immunoprecipitation assays confirmed that TUG1 directly bound to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and elevated Nrf2 protein expression. Moreover, Nrf2-neutralizing antibody effectively reversed the TUG1 overexpression-mediated promotion of ESCC cell resistance to DDP. In conclusion, our findings demonstrated that TUG1 promoted ESCC cell resistance to DDP, at least in part, through upregulating Nrf2.