A zinc finger family protein, ZNF263, promotes hepatocellular carcinoma resistance to apoptosis via activation of ER stress-dependent autophagy

Jie Cui; Jiatao Liu; Lulu Fan; Yue Zhu; Bei Zhou; Yu Wang; Wei Hua; Wei Wei; Guoping Sun

doi:10.1016/j.tranon.2020.100851

A zinc finger family protein, ZNF263, promotes hepatocellular carcinoma resistance to apoptosis via activation of ER stress-dependent autophagy

Transl Oncol. 2020 Dec;13(12):100851. doi: 10.1016/j.tranon.2020.100851. Epub 2020 Sep 6.

Authors

Jie Cui¹, Jiatao Liu², Lulu Fan¹, Yue Zhu¹, Bei Zhou¹, Yu Wang¹, Wei Hua³, Wei Wei⁴, Guoping Sun⁵

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
² Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China; Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
³ Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
⁴ Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
⁵ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China. Electronic address: sungp@ahmu.edu.cn.

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.