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<scp>EZH2</scp> promotes the progression of osteosarcoma through the activation of the <scp>AKT</scp> / <scp>GSK3β</scp> pathway

Authors :
Dongdong, Wan
Xiuxin, Han
Chao, Zhang
Yan, Zhang
Yulin, Ma
Guowen, Wang
Source :
Clinical and Experimental Pharmacology and Physiology. 49:1179-1186
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

Enhancer of zeste homologue 2 (EZH2) is a clarified promoter in a list of tumours, including osteosarcoma (OS). Our research was projected to define the mechanism involved in EZH2-mediated OS progression through the protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) pathway. EZH2 expression was tested in 66 OS tissues and five osteosarcoma cell lines (143B, SJSA-1, HOS, MG63, and U2OS). In HOS and U2OS cells, cellular malignant characteristics, and the markers of the AKT/GSK3β signalling pathway were measured when EZH2 was silenced or overexpressed. Meanwhile, rescue assays were implemented to observe whether the AKT/GSK3β signalling pathway inhibitor (MK-2206) could affect the role of overexpressed EZH2 in OS cells. EZH2 was up-regulated in tumour tissues of OS patients. OS cell lines (HOS and U2OS) showed impairments of proliferative, migratory, invasive and anti-apoptotic properties when EZH2 was silenced. Downregulated EZH2 inhibited the activation of the AKT/GSK3 signalling pathway. However, the situation in HOS and U2OS cells over-expressing EZH2 was opposite. MK-2206 erased EZH2 up-regulation-induced promotion of OS cell growth. It is demonstrated that EZH2 promotes the progression of OS via inducing the activation of the AKT/GSK3β pathway, offering a therapeutic direction for OS treatment.

Details

ISSN :
14401681 and 03051870
Volume :
49
Database :
OpenAIRE
Journal :
Clinical and Experimental Pharmacology and Physiology
Accession number :
edsair.doi.dedup.....22535b724db0ab5bd8a3b29090451a73