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

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.

Antigen processing and presentation‐related signature‐derived BNIP3 is a novel oncogene and immunotherapy determinant in osteosarcoma based on machine learning and in vitro validation

“…AMG, in combination with Rapamycin, showed efficacy in osteosarcoma 26 . MK was proven to affect the role of overexpressed EZH2 in osteosarcoma 27 …”

“…26 MK was proven to affect the role of overexpressed EZH2 in osteosarcoma. 27 Among the five included genes in the APP-related score, miR-627-3p, targeting PTN, inhibited osteosarcoma proliferation and metastasis. 28 SSX1 could increase epithelial features and inhibit osteosarcoma metastasis.…”

EZH2 Gene Knockdown Inhibits Sheep Pituitary Cell Proliferation via Downregulating the AKT/ERK Signaling Pathway

“…Although the processes through which EZH2 functions as a transcription factor have yet to be elucidated, there is evidence to suggest that multiple signaling pathways may be involved [ 43 ]. For example, EZH2 promotes OS progression via the AKT/GSK3β pathway [ 44 ], and it enhances cell proliferation and migration in trophoblast cell lines by modulating functions in the p38/MAPK signaling pathway [ 45 ]. Additionally, EZH2 has actions that induce the PI3K/AKT pathway in clinically aggressive chronic lymphocytic leukemia [ 46 ], and it modulates the cardioprotective effects of mesenchymal-stem-cell-secreted exosomes via HMGA2-mediated PI3K/AKT signaling [ 19 ].…”