Overexpression of LINC00551 promotes autophagy-dependent ferroptosis of lung adenocarcinoma via upregulating DDIT4 by sponging miR-4328

PeerJ

article

Xiong Peng¹  Rui Yang³  Weilin Peng¹  Zhenyu Zhao¹  Guangxu Tu¹  Boxue He¹  Qidong Cai¹  Shuai Shi¹  Wei Yin¹  Fenglei Yu¹  Yongguang Tao¹  Xiang Wang¹ 

[1] Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University;Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, the Second Xiangya Hospital of Central South University;Department of Pathology, School of Basic Medicine and Xiangya Hospital, Central South University;NHC Key Laboratory of Carcinogenesis ,(Central South University), Cancer Research Institute and School of Basic Medicine, Central South University;Department of Pathology, Xiangya Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Central South University

关键词: LINC00551;    DDIT4;    Ferroptosis;    Autophagy;    Lung adenocarcinoma;   

DOI  :  10.7717/peerj.14180

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

According to mounting evidence, long noncoding RNAs (lncRNAs) play a vital role in regulated cell death (RCD). A potential strategy for cancer therapy involves triggering ferroptosis, a novel form of RCD. Although it is thought to be an autophagy-dependent process, it is still unclear how the two processes interact. This study characterized a long intergenic noncoding RNA, LINC00551, expressed at a low level in lung adenocarcinoma (LUAD) and some other cancers. Overexpression of LINC00551 suppresses cell viability while promoting autophagy and RSL-3-induced ferroptosis in LUAD cells. LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes LUAD autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. This study provided an insight into the molecular mechanism regulating ferroptosis and highlighted LINC00551 as a potential therapeutic target for LUAD.

【 授权许可】

CC BY