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

Dongdong Wan,Xiuxin Han,Chao Zhang,Yan Zhang,Yulin Ma,Guowen Wang

Published 2022 in Clinical and Experimental Pharmacology and Physiology

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.

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