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...
Main Authors: | , , , , , |
---|---|
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 |