A Zinc Finger Family Protein, ZNF263, Promotes Hepatocellular Carcinoma Resistance to Apoptosis Via Activation of ER Stress-dependent Autophagy

Overview

Journal Transl Oncol

Specialty Oncology

Date 2020 Sep 8

PMID 32898766

Citations 15

Authors

Jie Cui

Jiatao Liu

Lulu Fan

Yue Zhu

Bei Zhou

Yu Wang

Wei Hua

Wei Wei

Guoping Sun

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Endoplasmic reticulum stress (ERS) is generally activated in HCC and is important for the sensitivity of HCC to anticancer drugs. ERS-dependent autophagy is a crucial mechanism affecting the sensitivity of HCC to anticancer drugs, but the mechanism by which ERS regulates autophagy is not well understood. Zinc finger protein 263 (ZNF263) is a transcription factor member of the zinc finger family. However, its functional role in HCC remains to be studied. In the current study, we investigated the role of ZNF263 in regulating ERS-induced chemoresistance in HCC and its possible mechanism. We found that ZNF263 was the most significant ERS-specific super-enhancer bounding transcriptional factor and was up-regulated in HCC patients and cell lines. Further, ZNF263 expression correlated with ERS, clinical stage and shorter survival in HCC patients. ZNF263 knockdown by RNA interference results in decreased proliferation, apoptosis resistance, and chemoresistance. Further study showed that ZNF263 increased chemoresistance by activating ERS-related autophagy. In conclusion, our study highlights ZNF263 as a functional ERS-related tumor activator and indicates it as a potential target for HCC therapy.

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