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COL11A1在泛癌中的致癌作用的生物信息学分析及实验验证

Bioinformatics analysis and experimental validation of the oncogenic role of COL11A1 in pan-cancer.

作者信息

Wan Xiaofeng, Deng Qingmei, Chen Anling, Zhang Xinhui, Yang Wulin

机构信息

Department of Laboratory, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui China.

Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031 Anhui China.

出版信息

3 Biotech. 2024 Dec;14(12):290. doi: 10.1007/s13205-024-04133-0. Epub 2024 Nov 4.

Abstract

The intricate expression patterns and oncogenic attributes of COL11A1 across different cancer types remain largely elusive. This study used several public databases (TCGA, GTEx, and CCLE) to investigate the pan-cancer landscape of COL11A1 expression, its prognostic implications, interplay with the immune microenvironment, and enriched signaling cascades. Concurrently, western blot analyses were performed to verify COL11A1 expression in lung adenocarcinoma (LUAD) cell lines and clinical samples. In addition, COL11A1 knockout cell lines were generated to scrutinize the functional consequences of COL11AI expression on cancer cell behavior by use MTT, colony formation, and scratch wound healing assays. A comprehensive database investigation revealed that COL11A1 was upregulated in a majority of tumor tissues and its expression was highly correlated with a patient's prognosis. Notably, genetic alterations in predominantly occurred as mutations, while its DNA methylation status inversely mirrored gene expression levels across multiple promoter regions. Our findings suggest that COL11A1 helps to modulate the tumor immune landscape and potentially acts through the epithelial-mesenchymal transition (EMT) pathway to exert its oncogenic function. Western blot analyses further substantiated the specific upregulation of COL11A1 in LUAD cell lines and tissues, suggesting a close association with the EMT process. Ablation of COL11A1 in cancer cells significantly reduced their proliferative, clonogenic, and migratory abilities, underscoring the functional significance of COL11A1 in tumor cell behavior. Collectively, this research revealed the prevalent overexpression of COL11A1 in pan-cancer tissues, its profound prognostic and microenvironmental correlations, and the mechanistic underpinnings of its tumor-promoting effects as mediated via EMT signaling. Our findings suggest that COL11A1 could serve as a prognostic and diagnostic biomarker and therapeutic target for cancer.

摘要

COL11A1在不同癌症类型中的复杂表达模式和致癌特性在很大程度上仍不清楚。本研究使用了几个公共数据库(TCGA、GTEx和CCLE)来研究COL11A1表达的泛癌格局、其预后意义、与免疫微环境的相互作用以及富集的信号级联反应。同时,进行蛋白质印迹分析以验证COL11A1在肺腺癌(LUAD)细胞系和临床样本中的表达。此外,通过使用MTT、集落形成和划痕伤口愈合试验,生成了COL11A1基因敲除细胞系,以仔细研究COL11AI表达对癌细胞行为的功能影响。一项全面的数据库调查显示,COL11A1在大多数肿瘤组织中上调,其表达与患者预后高度相关。值得注意的是,主要发生的基因改变为突变,而其DNA甲基化状态在多个启动子区域与基因表达水平呈负相关。我们的研究结果表明,COL11A1有助于调节肿瘤免疫格局,并可能通过上皮-间质转化(EMT)途径发挥其致癌功能。蛋白质印迹分析进一步证实了COL11A1在LUAD细胞系和组织中的特异性上调,表明其与EMT过程密切相关。癌细胞中COL11A1的缺失显著降低了它们的增殖、克隆形成和迁移能力,突出了COL11A1在肿瘤细胞行为中的功能重要性。总体而言,这项研究揭示了COL11A1在泛癌组织中的普遍过表达、其与预后和微环境的深刻相关性,以及其通过EMT信号介导的促肿瘤作用的机制基础。我们的研究结果表明,COL11A1可作为癌症的预后和诊断生物标志物以及治疗靶点。

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