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Esophageal 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 resistancerelated P-gp.In contrast,TUG1 knockdown exerted an opposite effect.Mechanistically,RNA pulldown 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 DDR In conclusion,our findings demonstrated that TUG1 promoted ESCC cell resistance to DDP,at least in part,through upregulating Nrf2.