LncRNA-XIST Promotes Lung Adenocarcinoma Growth and Inhibits Ferroptosis by Regulating GPX4

Chen-Lin Lu; Jie Liu; Jun-Fa Yang

doi:10.1007/s12033-023-00993-8

LncRNA-XIST Promotes Lung Adenocarcinoma Growth and Inhibits Ferroptosis by Regulating GPX4

Mol Biotechnol. 2023 Dec 28. doi: 10.1007/s12033-023-00993-8. Online ahead of print.

Authors

Chen-Lin Lu¹, Jie Liu², Jun-Fa Yang³

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, China.
² Department of Orthopedics, The Affiliated Taizhou People's Hospital of Nanjing Medical University Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, China.
³ Department of Respiratory and Critical Care Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, China. yangjunfa2011@163.com.

PMID: 38153663
DOI: 10.1007/s12033-023-00993-8

Abstract

This study aimed to explore the regulatory effects and molecular mechanisms of long non-coding RNA X-inactive-specific transcript (LncRNA-XIST) in lung adenocarcinoma. si-XIST or glutathione peroxidase 4 (GPX4) plasmids were transfected in PC-9 cells to suppress LncRNA-XIST expression or over-express GPX4, respectively. The mRNA expression levels of LncRNA-XIST and GPX4 in lung adenocarcinoma tissues or cells were assessed using RT-qPCR. CCK-8 assay was performed to examine cell activity, and corresponding biochemical kits were used to measure the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA) in cells. Western blot is used to examine relative protein expression of FANCD2, SLC7A11, and GPX4 in lung adenocarcinoma cells. The mRNA and protein expression levels of LncRNA-XIST in clinical tissues and cells of lung adenocarcinoma were significantly higher than those in adjacent tissues and normal cells. Functional analysis showed that knockdown of LncRNA-XIST notably weakened the viability of lung adenocarcinoma cells and promoted ferroptosis (manifested by significantly up-regulated levels of ROS, MDA, and Fe²⁺ and down-regulated the expression of SLC7A11 and FANCD2, P < 0.05). Further mechanism analysis revealed that knockdown of LncRNA-XIST markedly inhibited the expression of GPX4 in lung adenocarcinoma cells and that GPX4 was significantly over-expressed in clinical tissues and cells of lung adenocarcinoma. Notably, the expression of GPX4 was positively correlated with that of LncRNA-XIST. Over-expression of GPX4 remarkably promoted cell proliferation and inhibited ferroptosis in lung adenocarcinoma. Besides, the GPX4 over-expression reversed the LncRNA-XIST knockdown-induced ferroptosis and decrease in lung adenocarcinoma cell viability. LncRNA-XIST increases the activity of lung adenocarcinoma cells and inhibits ferroptosis by up-regulating GPX4. Knocking down LncRNA-XIST may be an effective treatment for lung adenocarcinoma.

Keywords: Ferroptosis; Glutathione peroxidase 4 (GPX4); Long non-coding RNA X-inactive-specific transcript (LncRNA-XIST); Lung adenocarcinoma.