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02 21, 2024;7 (1): 215.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR.

Dong-Min Liang, You-Jie Li, Jia-Xiang Zhang, Huan-Huan Shen, Chun-Xia Wu, Ning Xie, Yan Liang, Yan-Mei Li, Jiang-Nan Xue, Hong-Fang Sun, Qin Wang, Jian Yang, Xiao-Hua Li, Ping-Yu Wang, Shu-Yang Xie
Author Information
  1. Dong-Min Liang: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  2. You-Jie Li: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  3. Jia-Xiang Zhang: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  4. Huan-Huan Shen: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  5. Chun-Xia Wu: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  6. Ning Xie: Department of Chest Surgery, Yantaishan Hospital, Yantai, Shandong, 264000, PR China.
  7. Yan Liang: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  8. Yan-Mei Li: Department of Immune Rheumatism, Yantaishan Hospital, Yantai, Shandong, 264000, PR China.
  9. Jiang-Nan Xue: Department of Immunology, Binzhou Medical University, Yantai, Shandong, 264003, PR China.
  10. Hong-Fang Sun: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  11. Qin Wang: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China.
  12. Jian Yang: Yantai Central Blood Station, Yantai, Shandong, 264003, PR China.
  13. Xiao-Hua Li: Yantai Central Blood Station, Yantai, Shandong, 264003, PR China.
  14. Ping-Yu Wang: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China. wangpingyu@bzmc.edu.cn. ORCID
  15. Shu-Yang Xie: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, PR China. xieshuyang@bzmc.edu.cn. ORCID
PMID: 38383737 DOI: 10.1038/s42003-024-05854-x

Abstract

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

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Grants

  1. 81772281/National Natural Science Foundation of China (National Science Foundation of China)

MeSH Term

Humans
Adenine
Autophagy
Carcinoma, Non-Small-Cell Lung
CD47 Antigen
Cell Line, Tumor
Cell Proliferation
Intracellular Signaling Peptides and Proteins
Lung Neoplasms
Macrophages
MicroRNAs
Phagocytosis
RNA, Long Noncoding

Chemicals

6-methyladenine
Adenine
CD47 Antigen
CD47 protein, human
Intracellular Signaling Peptides and Proteins
MicroRNAs
RNA, Long Noncoding
TIPRL protein, human
KCTD21 protein, human
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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