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

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

  • FASEB J. 2024 Dec 15;38(23):e70221. doi: 10.1096/fj.202400951R.
Hong Huang 1 2,  Yan Wang 3,  Jiadi Gan 4,  Hong Bu 2 5,  Cong Li 3,  Yi Li 3,  Yongfeng Yang 1,  Dan Liu 4
Affiliations

Affiliations

  • 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.
PMID: 39625368 DOI: 10.1096/fj.202400951R
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.

Keywords

FRK; NQO2; NSCLC; exosome; miR‐9‐3p; mitochondria.

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