Shen Yi, Li Jun, Peng Dan, Liao Lele, Chen Xia, Zhong Weiye, Liu Zicheng, Yu Chao, Sun Yuanliang
Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
Department of Spine Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China.
Genes Dis. 2022 Aug 6;10(5):2125-2136. doi: 10.1016/j.gendis.2022.06.010. eCollection 2023 Sep.
Osteosarcoma is a common malignant tumor occurring in children and young adults. Chondroitin sulfate (CS) participates in cell adhesion, cell division, and the formation of neural networks in the body, the biosynthesis of which requires the participation of glycosyltransferases. CHPF, a glycosyltransferase, plays a role in the extension of CS. Recently, CHPF's biological roles and functional importance in human diseases including malignant tumors have been widely discussed. However, whether CHPF is involved in osteosarcoma development and growth has not been revealed. The present work aimed to investigate the expression levels, functional significance and molecular mechanism of CHPF in osteosarcoma progression. Our results revealed that CHPF is strongly expressed in osteosarcoma tissues and cells. Furthermore, CHPF serves as a tumor promoter in the development and progression of osteosarcoma through enhancing cell proliferation and migration while suppressing apoptosis. Exploration of the mechanism by which CHPF promotes osteosarcoma indicated that CHPF promotes osteosarcoma through counteracting SKP2's ubiquitination and activating the Akt signaling pathway. For the first time, we clarified the roles of CHPF in osteosarcoma, and our results suggested that CHPF might be a novel therapeutic target in the treatment strategies for osteosarcoma.
骨肉瘤是一种常见于儿童和年轻人的恶性肿瘤。硫酸软骨素(CS)参与体内细胞黏附、细胞分裂和神经网络的形成,其生物合成需要糖基转移酶的参与。CHPF作为一种糖基转移酶,在CS的延伸过程中发挥作用。最近,CHPF在包括恶性肿瘤在内的人类疾病中的生物学作用和功能重要性受到了广泛讨论。然而,CHPF是否参与骨肉瘤的发生和发展尚未明确。本研究旨在探讨CHPF在骨肉瘤进展中的表达水平、功能意义和分子机制。我们的结果显示,CHPF在骨肉瘤组织和细胞中高表达。此外,CHPF通过增强细胞增殖和迁移同时抑制细胞凋亡,在骨肉瘤的发生和发展中起到肿瘤促进作用。对CHPF促进骨肉瘤机制的探索表明,CHPF通过对抗SKP2的泛素化并激活Akt信号通路来促进骨肉瘤。我们首次阐明了CHPF在骨肉瘤中的作用,结果表明CHPF可能是骨肉瘤治疗策略中的一个新的治疗靶点。