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

Abstract 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.