M2 macrophage exosomal LINC01001 promotes non-small cell lung cancer development by affecting METTL3 and glycolysis pathway

• Published in: Cancer gene therapy Vol. 30; no. 11; pp. 1569 - 1580
• Main Authors: Xu, Li, Li, Kang, Li, Jia, Xu, Fang, Liang, Shuzhi, Kong, Yi, Chen, Bolin
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2023; Nature Publishing Group
• Subjects: 13/100; 13/51; 631/67/1612/1350; 64/60; 692/53; 96/31; Animals; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Carcinoma, Non-Small-Cell Lung - genetics; Cell growth; Cell proliferation; DNA methylation; Exosomes; Gene Expression; Gene Therapy; Glycolysis; Lactic Acid; Lung cancer; Lung Neoplasms - genetics; Lymphocytes T; Macrophages; Mice; Non-small cell lung carcinoma; Small cell lung carcinoma; Tumorigenesis
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-023-00661-8

There have been data showing that LINC01001 is highly expressed in lung cancer, but the effect of M2 macrophage exosomal LINC01001 to METTL3, glycolysis and immunity in non-small cell lung cancer (NSCLC) has not been reported. In this study, we aimed to explore the regulatory effect and mechanism of M2 macrophage exosomal LINC01001 in NSCLC. The results of our study show that the verification of macrophage exosomes, it was confirmed that exosomes regulated proliferation, glucose intake, lactate production and ATP levels of NSCLC cells. Exosomes also promoted the expression of METTL3. Bioinformatics screening showed that LINC01001 regulated METTL3. Subsequent experiments revealed exosomal LINC01001 influenced the glycolysis processes of NSCLC cells. Through RIP, it was proved that LINC01001 functioned in combination with METTL3. Bioinformatics predicted that NASP was a METTL3-targeted gene. LINC01001 could also regulate NASP methylation. Tumorigenesis in mice also indicated that LINC01001 mediated METTL3 to stimulate the development of tumors. In this study, LINC01001 was successfully verified in the exosomes-derived from M2 macrophages. It was confirmed that LINC01001 could interact with METTL3 and regulate glycolysis process in NSCLC cells. LINC01001 also inhibited T cell proliferation.