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FRK exerts oncogenic effects by targeting NQO2 via exosomal miR-9-3p to regulate mitochondrial function

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机构： [1]Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Institute of Clinical Pathology, Key Laboratory of Transplantation Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [3]Research Core Facility of West China Hospital, Sichuan University, Chengdu, Sichuan, China. [4]Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [5]Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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关键词： exosome FRK miR-9-3p mitochondria NQO2 NSCLC

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The role of Fyn-related kinase (FRK) in promoting tumor progression and metabolism in non-small cell lung cancer (NSCLC) has been demonstrated in our earlier study, and here we further explored whether exosome could serve as a key player in the relevant regulatory mechanism. Exosomes were isolated from the culture medium of FRK-knockout (KO) cells and co-cultured with NSCLC cells, showing negative effects on cell proliferation, metastasis, metabolism, and mitochondrial function. Exosomal miR-9-3p was selected as an intermediate messenger through microRNA (miRNA) sequencing. The miR-9-3p inhibitor and exosome inhibitor GW4869 were then applied in the co-culture system to verify the contribution of exosomal miR-9-3p to cell malignant phenotype and mitochondrial function. Moreover, NQO2, a potential target of exosomal miR-9-3p, was also suggested to be involved in the regulation of mitochondrial functional status. In brief, this study revealed a novel molecular mechanism by which FRK promotes the malignant progression of NSCLC by targeting NQO2 via exosomal miR-9-3p to strengthen mitochondrial function.© 2024 Federation of American Societies for Experimental Biology.

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大类 | 2 区

生物学

小类 | 2 区生化与分子生物学 2 区生物学 3 区细胞生物学

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第一作者机构： [1]Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Institute of Clinical Pathology, Key Laboratory of Transplantation Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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