2. Academic Validation
  3. LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells

LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells

  • Sci Rep. 2019 Nov 7;9(1):16185. doi: 10.1038/s41598-019-52837-8.
Wenchuan Qi 1,  Zhenhua Li 2,  Longjiang Xia 3,  Jiangshan Dai 1,  Qiao Zhang 4,  Chuanfang Wu 1,  Si Xu 5 6
Affiliations

Affiliations

  • 1 Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, 610065, Chengdu, Sichuan, P.R. China.
  • 2 Affiliated Hospital of Changchun University of Traditional Chinese Medicine, 130117, Changchun, Jilin, P.R. China.
  • 3 Chengdu University of Traditional Chinese Medicine, 611130, Chengdu, Sichuan, P.R. China.
  • 4 China-Japan Union Hospital of Jilin University, 130033, Changchun, Jilin, P.R. China.
  • 5 Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, 610065, Chengdu, Sichuan, P.R. China. [email protected].
  • 6 Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, 610072, Chengdu, Sichuan, P.R. China. [email protected].
PMID: 31700067 DOI: 10.1038/s41598-019-52837-8
Abstract

Ferroptosis is a non-apoptotic, iron-dependent oxidative form of cell death that is specifically induced by erastin in Ras mutant Cancer cells. Ferroptotic cell death is the result of membrane lipid peroxide damage caused by the accumulation of hydroxyl radicals derived from H2O2 by the Fenton reaction. Peroxidases are key cellular antioxidant enzymes that block such damaging processes. Few studies have examined the roles of long non-coding RNAs (lncRNAs) in the regulation of cellular oxidative stress, especially in Ferroptosis. Here, we demonstrated that erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. Such effects critically inhibited the cellular antioxidant capacity and cell viability. Additionally, high expression levels of GABPB1 were correlated with poor prognosis of hepatocellular carcinoma (HCC) Patients, while high GABPB1-AS1 levels in HCC patients correlated with improved overall survival. Collectively, these data demonstrate a mechanistic link between GABPB1 and its antisense lncRNA GABPB1-AS1 in erastin-induced Ferroptosis and establish GABPB1 and GABPB1-AS1 as attractive therapeutic targets for HCC.

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