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Research Paper|Volume 13, Issue 3|pp 4468—4481

PRMT5 regulates colorectal cancer cell growth and EMT via EGFR/Akt/GSK3β signaling cascades

Yongrong Yan1,2, Peipei Zhao1,2, Zihuan Wang3, Zhen Liu4, Zhizhi Wang3, Jinglan Zhang3, Yanqing Ding1,2, Xing Hua4, Lina Yu1,2
  • 1Department of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangzhou 510515, Guangdong Province, People’s Republic of China
  • 2Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, Guangdong Province, People’s Republic of China
  • 3The First Clinical Medical Department, Southern Medical University, Guangzhou 510515, Guangdong Province, People’s Republic of China
  • 4Department of Pathology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, Guangdong Province, People’s Republic of China
Received: August 26, 2020Accepted: October 9, 2020Published: January 20, 2021
https://doi.org/10.18632/aging.202407

Copyright: © 2021 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Emerging evidence shows that type II protein arginine methyltransferase 5 (PRMT5) serves as an oncoprotein and plays a critical role in many types of human cancer. However, the precise role and function of PRMT5 in human colorectal cancer (CRC) growth and epithelial-mesenchymal transition (EMT) are still unclear, and the related molecular mechanism and signaling axis remains largely obscure. Here, we show that PRMT5 is highly expressed in CRC cell lines and tissues. Using PRMT5 stable depletion cell lines and specific inhibitor, we discover that down-regulation of PRMT5 by shRNA or inhibition of PRMT5 activity by specific inhibitor GSK591 markedly suppresses CRC cell proliferation and cell cycle progression, which is closely associated with PRMT5 enzyme activity. Moreover, PRMT5 regulates CRC cell growth and cycle progression via activation of Akt, but not through ERK1/2, PTEN, and mTOR signaling pathway. Further study shows that PRMT5 controls EMT of CRC cells by activation of EGFR/Akt/GSK3β signaling cascades. Collectively, our results reveal that PRMT5 promotes CRC cell proliferation, cell cycle progression, and EMT via regulation of EGFR/Akt/GSK3β signaling cascades. Most importantly, our findings also suggest that PRMT5 may be a potential therapeutic target for the treatment of human colorectal cancer.