COL12A1 通过 FAK/PI3K/AKT/mTOR 通路促进骨肉瘤进展

IF 2.2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Yun-Pu Zhang, Hai-Xia Wang, Zhi-Chao Gao, Li-Zhe Xu, Yu Fu
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引用次数: 0

摘要

背景:骨肉瘤(OS)是青少年和儿童中常见的恶性肿瘤:目的:本研究旨在探讨COL12A1(一种在各种癌症中经常过度表达并与不良预后相关的基因)在OS进展中的作用,并探索其潜在机制:方法:通过生物信息学分析、临床样本检查和OS细胞系评估COL12A1在OS中的表达模式和潜在功能。方法:通过生物信息学分析、临床样本检查和OS细胞系,评估了COL12A1在OS中的表达模式和潜在功能。进行了各种检测,包括Transwell、CCK-8、流式细胞术和伤口愈合,以评估COL12A1对OS细胞生长、细胞周期进展、细胞凋亡、侵袭和迁移的影响。结果发现,COL12A1在OS细胞中的表达量显著增加:结果:COL12A1在OS组织和细胞中的表达明显升高。COL12A1的上调可促进细胞生长、加速细胞周期进展、增强迁移和侵袭,同时抑制细胞凋亡。相反,敲除 COL12A1 则会产生相反的效果。此外,COL12A1 的过表达增加了 FAK/PI3K/AKT/mTOR 通路中成分的磷酸化。FAK抑制剂Y15减轻了COL12A1过表达对OS中细胞凋亡、侵袭、增殖和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通路促进了OS的发展,这表明COL12A1可作为一种有价值的生物标志物用于预测和识别OS患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
COL12A1 Promotes Osteosarcoma Progression via the FAK/PI3K/AKT/mTOR Pathway.

Background: Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy.

Aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊
Current molecular medicine
Current molecular medicine 医学-医学:研究与实验
CiteScore
5.00
自引率
4.00%
发文量
141
审稿时长
4-8 weeks
期刊介绍: Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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