PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis

Technol Cancer Res Treat. 2023 Jan-Dec:22:15330338231161139. doi: 10.1177/15330338231161139.

Abstract

Objectives: This study aims to investigate the function of the protein arginine methyltransferase 5 (PRMT5) and fibroblast growth factor receptor 3 (FGFR3)/Akt signaling axis in the epithelial-mesenchymal transition (EMT) of human lung cancer. Methods: The mRNA and protein expression levels of PRMT5, FGFR3, p-Akt, and EMT markers are determined by quantitative real-time PCR and Western blotting, respectively; the expression and localization of PRMT5, p-Akt, and proliferating cell nuclear antigen are detected by immunofluorescence; the human lung cancer cell proliferation is measured by MTS assay. Results: PRMT5 and FGFR3 are highly expressed in human lung cancer tissues and are closely related to lymphatic metastasis. Moreover, down-regulation of PRMT5 by lentivirus-mediated shRNAs or inhibition of PRMT5 by specific inhibitors attenuates FGFR3 expression, Akt phosphorylation, and lung cancer cell proliferation. Further studies show that silencing PRMT5 impairs EMT-related markers, including vimentin, collagen I, and β-catenin. Conversely, ectopic expression of PRMT5 increases FGFR3 expression, Akt phosphorylation, and EMT-related markers, suggesting that PRMT5 regulates metastasis probably through the FGFR3/Akt signaling axis. Conclusion: PRMT5/FGFR3/Akt signaling axis controls human lung cancer progression and metastasis and also implies that PRMT5 may serve as a prognostic biomarker and therapeutic candidate for treating lung cancer.

Keywords: AKT; EMT; FGFR3; PRMT5; lung cancer; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lung Neoplasms* / pathology
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RNA, Small Interfering / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Signal Transduction / genetics

Substances

  • Proto-Oncogene Proteins c-akt
  • Receptor, Fibroblast Growth Factor, Type 3
  • RNA, Small Interfering
  • FGFR3 protein, human
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases