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

Xiong Peng; Rui Yang; Weilin Peng; Zhenyu Zhao; Guangxu Tu; Boxue He; Qidong Cai; Shuai Shi; Wei Yin; Fenglei Yu; Yongguang Tao; Xiang Wang

doi:10.7717/peerj.14180

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

PeerJ. 2022 Oct 12:10:e14180. doi: 10.7717/peerj.14180. eCollection 2022.

Authors

Xiong Peng^{1

2}, Rui Yang³, Weilin Peng^{1

2}, Zhenyu Zhao^{1

2}, Guangxu Tu^{1

2}, Boxue He^{1

2}, Qidong Cai^{1

2}, Shuai Shi^{1

2}, Wei Yin^{1

2}, Fenglei Yu^{1

2}, Yongguang Tao^{1

4

5}, Xiang Wang^{1

2}

Affiliations

¹ Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
² Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
³ Department of Pathology, School of Basic Medicine and Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, China.
⁵ Department of Pathology, Xiangya Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Central South University, Changsha, Hunan, China.

Abstract

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.

Keywords: Autophagy; DDIT4; Ferroptosis; LINC00551; Lung adenocarcinoma.

Publication types

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

MeSH terms

Adenocarcinoma* / genetics
Autophagy / genetics
Cell Proliferation / genetics
Ferroptosis* / genetics
Humans
Lung / metabolism
Lung Neoplasms* / drug therapy
MicroRNAs* / genetics
Transcription Factors

Substances

MicroRNAs
DDIT4 protein, human
Transcription Factors

Grants and funding

This work was supported by the National Natural Science Foundation of China (81972195 Fenglei Yu; 82072594, Yongguang Tao; 82172879, Li Wang, project leader), the Hunan Provincial Key Area R&D Programs (2020SK53424, Xiang Wang), the Nature Science Foundation of Hunan Province (2021JJ30957, Xiang Wang; 2022JJ30995, Wei Zhuang, project leader) and the Scientific Research Program of Hunan Provincial Health Commission (Grant Number 20201047, Xiang Wang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.