AUTHOR=Hong Lingling , Wang Xuehai , Cui Weiming , Wang Fengxu , Shi Weiwei , Yu Shali , Luo Yonghua , Zhong Lixin , Zhao Xinyuan 

TITLE=Construction of a ferroptosis scoring system and identification of LINC01572 as a novel ferroptosis suppressor in lung adenocarcinoma

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1098136

DOI=10.3389/fphar.2022.1098136

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Ferroptosis is a novel process of programmed cell death driven by excessive lipid peroxidation that is associated with the development of lung adenocarcinoma. N6-methyladenosine (m6a) modification of multiple genes is involved in regulating the ferroptosis process, while the predictive value of N6-methyladenosine- and ferroptosis-associated lncRNA (FMRlncRNA) in the prognosis of patients remains with LUAD remains unknown.</p><p><bold>Methods:</bold> Unsupervised cluster algorithm was applied to generate subcluster in LUAD according to ferroptosis-associated lncRNA. Stepwise Cox analysis and LASSO algorithm were applied to develop a prognostic model. Cellular location was detected by single-cell analysis. Also, we conducted Gene set enrichment analysis (GSEA) enrichment, immune microenvironment and drug sensitivity analysis. In addition, the expression and function of the LINC01572 were investigated by several <italic>in vitro</italic> experiments including qRT-PCR, cell viability assays and ferroptosis assays.</p><p><bold>Results:</bold> A novel ferroptosis-associated lncRNAs-based molecular subtype containing two subclusters were determined in LUAD. Then, we successfully created a risk model according to five ferroptosis-associated lncRNAs (LINC00472, MBNL1-AS1, LINC01572, ZFPM2-AS1, and TMPO-AS1). Our nominated model had good stability and predictive function. The expression patterns of five ferroptosis-associated lncRNAs were confirmed by polymerase chain reaction (PCR) in LUAD cell lines. Knockdown of LINC01572 significantly inhibited cell viability and induced ferroptosis in LUAD cell lines.</p><p><bold>Conclusion:</bold> Our data provided a risk score system based on ferroptosis-associated lncRNAs with prognostic value in LUAD. Moreover, LINC01572 may serve as a novel ferroptosis suppressor in LUAD.</p>