LncRNA HEPFAL accelerates ferroptosis in hepatocellular carcinoma by regulating SLC7A11 ubiquitination

Baofu Zhang; Wenming Bao; Sina Zhang; Bo Chen; Xiang Zhou; Jungang Zhao; Zhehao Shi; Tan Zhang; Ziyan Chen; Luhui Wang; Xiangtao Zheng; Gang Chen; Yi Wang

doi:10.1038/s41419-022-05173-1

LncRNA HEPFAL accelerates ferroptosis in hepatocellular carcinoma by regulating SLC7A11 ubiquitination

Cell Death Dis. 2022 Aug 25;13(8):734. doi: 10.1038/s41419-022-05173-1.

Authors

Baofu Zhang^{1

2

3}, Wenming Bao^{1

2}, Sina Zhang^{1

2}, Bo Chen^{1

2}, Xiang Zhou^{1

2}, Jungang Zhao^{1

2}, Zhehao Shi^{1

2}, Tan Zhang^{1

2}, Ziyan Chen^{1

2}, Luhui Wang^{1

2}, Xiangtao Zheng⁴, Gang Chen^{5

6}, Yi Wang⁷

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
³ Department of Vascular Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Vascular Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. vaszhengxiangtao@126.com.
⁵ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. chen.gang@wmu.edu.cn.
⁶ Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. chen.gang@wmu.edu.cn.
⁷ Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China. wang.yi@wmu.edu.cn.

Abstract

Ferroptosis is a new type of cell death that has been recognized in recent years and is different from apoptosis, autophagy, and necrosis. It is mainly due to cellular iron homeostasis and lipid peroxidation of iron metabolism caused by large accumulation. There is a close correlation between ferroptosis and hepatocellular carcinoma (HCC). This study shows that the expression of the long noncoding RNA HEPFAL was reduced in HCC tissues. We found that lncRNA HEPFAL can promote ferroptosis by reducing the expression of solute carrier family 7 member 11 (SLC7A11) and increasing the levels of lipid reactive oxygen species (ROS) and iron (two surrogate markers of ferroptosis). In addition, we found that lncRNA HEPFAL increases the sensitivity of erastin-induced ferroptosis, which may be related to mTORC1, and lncRNA HEPFAL can promote the ubiquitination of SLC7A11 and reduce the stability of the SLC7A11 protein, resulting in decreased expression. Understanding these mechanisms indicates that lncRNAs related to ferroptosis are essential for the occurrence and treatment of HCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Transport System y+ / genetics
Amino Acid Transport System y+ / metabolism
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / metabolism
Ferroptosis* / genetics
Humans
Iron / metabolism
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Ubiquitination

Substances

Amino Acid Transport System y+
RNA, Long Noncoding
SLC7A11 protein, human
Iron