Zhang Yun-Pu, Wang Hai-Xia, Gao Zhi-Chao, Xu Li-Zhe, Fu Yu
Department of Spine Surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, P.R.China.
Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P.R.China.
Curr Mol Med. 2024 Sep 13. doi: 10.2174/0115665240322280240903111159.
Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy.
This study aimed to investigate the role of COL12A1, a gene often overexpressed in various cancers and associated with poor prognosis, in the progression of OS and explore the underlying mechanisms.
The expression pattern and potential function of COL12A1 in OS were evaluated using bioinformatics analyses, clinical sample examination, and OS cell lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing, were performed to assess the impact of COL12A1 on OS cell growth, cell cycle progression, apoptosis, invasion, and migration. Western blot analysis was conducted to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway.
COL12A1 expression was significantly elevated in OS tissues and cells. Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression, and enhanced migration and invasion while inhibiting apoptosis. Conversely, the knockdown of COL12A1 had the opposite effect. Additionally, COL12A1 overexpression increased the phosphorylation of components in the FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the FAK/PI3K/AKT/mTOR pathway in OS.
Our findings indicated that COL12A1 enhanced OS development by activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve as a valuable biomarker for the prediction and identification of OS patients.
骨肉瘤（OS）是青少年和儿童中常见的恶性肿瘤，其特点是转移倾向高且对化疗耐药。
本研究旨在探讨COL12A1基因在骨肉瘤进展中的作用及其潜在机制，该基因在多种癌症中常过度表达且与预后不良相关。
采用生物信息学分析、临床样本检测和骨肉瘤细胞系评估COL12A1在骨肉瘤中的表达模式和潜在功能。进行了包括Transwell、CCK-8、流式细胞术和伤口愈合实验等多种检测，以评估COL12A1对骨肉瘤细胞生长、细胞周期进程、凋亡、侵袭和迁移的影响。通过蛋白质免疫印迹分析研究与FAK/PI3K/AKT/mTOR通路相关的标志物。
COL12A1在骨肉瘤组织和细胞中表达显著升高。COL12A1的上调促进细胞生长，加速细胞周期进程，增强迁移和侵袭能力，同时抑制细胞凋亡。相反，COL12A1基因敲低则产生相反的效果。此外，COL12A1的过表达增加了FAK/PI3K/AKT/mTOR通路中各组分的磷酸化水平。FAK抑制剂Y15减轻了COL12A1过表达对骨肉瘤细胞凋亡、侵袭、增殖以及FAK/PI3K/AKT/mTOR通路的影响。
我们的研究结果表明，COL12A1通过激活FAK/PI3K/AKT/mTOR通路促进骨肉瘤发展，提示COL12A1可作为预测和识别骨肉瘤患者的有价值生物标志物。
