2. Academic Validation
  3. Downregulation of N6-methyladenosine-modified LINC00641 promotes EMT, but provides a ferroptotic vulnerability in lung cancer

Downregulation of N6-methyladenosine-modified LINC00641 promotes EMT, but provides a ferroptotic vulnerability in lung cancer

  • Cell Death Dis. 2023 Jun 13;14(6):359. doi: 10.1038/s41419-023-05880-3.
Shu Xi # 1 2 3,  Dao-Jing Ming # 1 2,  Jin-Hui Zhang 1 2,  Meng-Meng Guo 1 2,  Shuang-Ying Wang 1,  Yi Cai 1,  Meng-Yang Liu 1,  Dan-Qi Wang 1,  Yi-Jie Zhang 4 5,  Yafei Li 6,  Shuai Yuan 7
Affiliations

Affiliations

  • 1 Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 2 School of Clinical Medicine, Henan University, Kaifeng, China.
  • 3 Department of Respiratory, Huaihe Hospital of Henan University, Kaifeng, China.
  • 4 School of Clinical Medicine, Henan University, Kaifeng, China. 13903782431@163.com.
  • 5 Department of Respiratory, Huaihe Hospital of Henan University, Kaifeng, China. 13903782431@163.com.
  • 6 Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China. liyafei2008@hotmail.com.
  • 7 Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. yuanshuai021@whu.edu.cn.
  • # Contributed equally.
PMID: 37311754 DOI: 10.1038/s41419-023-05880-3
Abstract

The prognosis of lung Cancer is poor with few effective therapies. Targeting Ferroptosis is a new promising strategy for Cancer therapy. LINC00641 has been involved in several cancers, however, its specific roles in lung Cancer treatment remain largely unknown. Here, we reported that LINC00641 was down-regulated in tumor tissues and its downregulation was associated with poor outcomes in lung adenocarcinoma. LINC00641 was localized primarily in the nucleus and was modified by m6A. The nuclear m6A reader YTHDC1 regulated LINC00641 expression by affecting its stability. We demonstrated that LINC00641 suppressed lung Cancer by inhibiting migration and invasion in vitro and metastasis in vivo. Knockdown of LINC00641 upregulated HuR protein level (especially in the cytoplasm), which subsequently increased N-Cadherin levels by stabilizing its mRNA, then ultimately promoted EMT. Interestingly, LINC00641 knockdown in lung Cancer cells increased the arachidonic acid metabolism and promoted Ferroptosis sensitivity. Our findings identified LINC00641 as a tumor suppressor through inhibiting EMT. In another aspect, low expression of LINC00641 caused a ferroptotic vulnerability in lung Cancer cells, which may serve as a potential ferroptosis-related therapeutic target for lung Cancer.

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