Ren Bingkai, Zheng Yibin, Nie Lizhong, Wu Fanhui, Huang Leiwen, Wei Jingdu, Yang Dong
Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Orthopedics, The Yiwu Central Hospital, Jinhua, Zhejiang, China.
J Oncol. 2023 Feb 23;2023:8454142. doi: 10.1155/2023/8454142. eCollection 2023.
GINS2 is overexpressed in several cancers, but little is known about its role in osteosarcoma (OS). A series of in vivo and in vitro experiments were conducted to explore the role of GINS2 in OS. In this study, we demonstrated that GINS2 was found to be highly expressed in OS tissues and cell lines, which was associated with poor outcomes in OS patients. GINS2 knockdown hindered the growth and induced apoptosis in OS cell lines in vitro. Furthermore, GINS2 knockdown effectively inhibited the growth of a xenograft tumor in vivo. By using an Affymetrix gene chip and intelligent pathway analysis, it was demonstrated that the GINS2 knockdown could reduce the expression of several targeted genes and reduce the activity of the MYC signaling pathway. Mechanically, LC-MS, CoIP, and rescue experiments revealed that GINS2 promoted tumor progression through the STAT3/MYC axis in the OS. Moreover, GINS2 was associated with tumor immunity and may be a potential immunotherapeutic target for OS.
GINS2在多种癌症中过表达，但其在骨肉瘤（OS）中的作用知之甚少。我们进行了一系列体内和体外实验来探究GINS2在OS中的作用。在本研究中，我们发现GINS2在OS组织和细胞系中高表达，这与OS患者的不良预后相关。在体外，敲低GINS2可抑制OS细胞系的生长并诱导其凋亡。此外，敲低GINS2可有效抑制体内异种移植肿瘤的生长。通过使用Affymetrix基因芯片和智能通路分析，表明敲低GINS2可降低多个靶向基因的表达并降低MYC信号通路的活性。从机制上讲，液相色谱-质谱联用（LC-MS）、免疫共沉淀（CoIP）和拯救实验表明，GINS2通过OS中的STAT3/MYC轴促进肿瘤进展。此外，GINS2与肿瘤免疫相关，可能是OS的潜在免疫治疗靶点。
