title: Egr-1 promotes hypoxia-induced autophagy to enhance chemo-resistance of hepatocellular carcinoma cells.
abstract: Previous studies suggest that early growth response gene-1 (Egr-1) plays an important role in hypoxia-induced drug-resistance. However, the mechanism still remains to be clarified. Herein, we investigated the role of Egr-1 in hypoxia-induced autophagy and its resulted hypoxia-driven chemo-resistance in Hepatocellular Carcinoma (HCC) cells. Our data demonstrated that Egr-1 was overexpressed in HCC tissues and cells and conferred them drug resistance under hypoxia. Mechanistically, Egr-1 transcriptionally regulated hypoxia-induced autophagy by binding to LC3 promoter in HCC cells, which resulted in resistance of HCC cells to chemotherapeutic agents; while dominant negative Egr-1 could inhibit autophagy level, and thus enhanced the sensitivity of HCC cells to chemotherapeutic agents, indicating that hypoxia-induced Egr-1 expression enhanced drug resistance of HCC cells likely through autophagy. Accordingly, it is suggested that a mechanism of hypoxia/Egr-1/autophagy axis might be involved in drug resistance in HCC.
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Wan-Xin
authors.initials: WX
authors.lastname: Peng
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Er-Meng
authors.initials: EM
authors.lastname: Xiong
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ge
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, PR China.
authors.forename: Yan-Ya
authors.initials: YY
authors.lastname: Wan
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, PR China.
authors.forename: Reyaz Ahmed
authors.initials: RA
authors.lastname: Bhat
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: ahg5@ujs.edu.cn.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Gong
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1
keywords: Autophagy; Chemo-resistance; Egr-1; HCC; Hypoxia