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

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...

Full description

Bibliographic Details
Main Authors: Yonghua Zheng MD, Jingjing Lu MD, Xiaoyan Hu MM, Xiaobiao Hu MB, Xiwen Gao MD, Jie Zhou MB
Format: Article
Language:English
Published: SAGE Publishing 2023-03-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/15330338231161139
_version_ 1797868085300953088
author Yonghua Zheng MD
Jingjing Lu MD
Xiaoyan Hu MM
Xiaobiao Hu MB
Xiwen Gao MD
Jie Zhou MB
author_facet Yonghua Zheng MD
Jingjing Lu MD
Xiaoyan Hu MM
Xiaobiao Hu MB
Xiwen Gao MD
Jie Zhou MB
author_sort Yonghua Zheng MD
collection DOAJ
description 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.
first_indexed 2024-04-09T23:51:34Z
format Article
id doaj.art-8ace2fb56750496db3b222684573a9be
institution Directory Open Access Journal
issn 1533-0338
language English
last_indexed 2024-04-09T23:51:34Z
publishDate 2023-03-01
publisher SAGE Publishing
record_format Article
series Technology in Cancer Research & Treatment
spelling doaj.art-8ace2fb56750496db3b222684573a9be2023-03-17T09:34:21ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382023-03-012210.1177/15330338231161139PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell MetastasisYonghua Zheng MD0Jingjing Lu MD1Xiaoyan Hu MM2Xiaobiao Hu MB3Xiwen Gao MD4Jie Zhou MB5 Department of Pulmonary Medicine, Shanghai Jinshan Tinglin Hospital, Shanghai, P.R. China Department of Pulmonary and Critical Care Medicine, , Tongji University School of Medicine, Shanghai, P.R. China Department of Pulmonary Medicine, Shanghai Jinshan Tinglin Hospital, Shanghai, P.R. China Department of Pulmonary Medicine, Shanghai Jinshan Tinglin Hospital, Shanghai, P.R. China Department of Pulmonary and Critical Care Medicine, Minhang Hospital, Fudan University, Shanghai, P.R. China Department of Pulmonary and Critical Care Medicine, Minhang Hospital, Fudan University, Shanghai, P.R. ChinaObjectives: 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.https://doi.org/10.1177/15330338231161139
spellingShingle Yonghua Zheng MD
Jingjing Lu MD
Xiaoyan Hu MM
Xiaobiao Hu MB
Xiwen Gao MD
Jie Zhou MB
PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis
Technology in Cancer Research & Treatment
title PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis
title_full PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis
title_fullStr PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis
title_full_unstemmed PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis
title_short PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis
title_sort prmt5 fgfr3 akt signaling axis facilitates lung cancer cell metastasis
url https://doi.org/10.1177/15330338231161139
work_keys_str_mv AT yonghuazhengmd prmt5fgfr3aktsignalingaxisfacilitateslungcancercellmetastasis
AT jingjinglumd prmt5fgfr3aktsignalingaxisfacilitateslungcancercellmetastasis
AT xiaoyanhumm prmt5fgfr3aktsignalingaxisfacilitateslungcancercellmetastasis
AT xiaobiaohumb prmt5fgfr3aktsignalingaxisfacilitateslungcancercellmetastasis
AT xiwengaomd prmt5fgfr3aktsignalingaxisfacilitateslungcancercellmetastasis
AT jiezhoumb prmt5fgfr3aktsignalingaxisfacilitateslungcancercellmetastasis