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

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.

• Authors: Yonghua Zheng, Jingjing Lu, Xiaoyan Hu, Xiaobiao Hu, Xiwen Gao, Jie Zhou
• Journal: Technology in cancer research & treatment (Technol Cancer Res Treat) 2023 Jan-Dec Vol. 22 Pg. 15330338231161139 ISSN: 1533-0338 [Electronic] United States
• PMID: 36927233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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