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Exp Cell Res. 2016 Jan 1;340(1):62-70. doi: 10.1016/j.yexcr.2015.12.006. Epub 2015 Dec 17.

Egr-1 promotes hypoxia-induced autophagy to enhance chemo-resistance of hepatocellular carcinoma cells.

Author information

1
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
2
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, PR China.
3
Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, PR China.
4
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: ahg5@ujs.edu.cn.

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.

KEYWORDS:

Autophagy; Chemo-resistance; Egr-1; HCC; Hypoxia

PMID:
26708617
DOI:
10.1016/j.yexcr.2015.12.006
[Indexed for MEDLINE]

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