背景:肾细胞癌(RCC)目前被认为是最常见的肾脏肿瘤。然而,转换因子诱导蛋白(TGFBI)的作用和潜在作用机制,一种细胞外基质蛋白,在RCC中仍然知之甚少。
方法:在本研究中,我们用了蛋白质印迹,定量实时聚合酶链反应(qRT-PCR),和免疫组织化学技术评估TGFBI在RCC组织或细胞中的表达。此外,我们使用CCK8,克隆,刮伤,和迁移测定。此外,我们通过流式细胞术检查了细胞凋亡和细胞周期进程,分析。最后,我们采用基因集富集分析(GSEA)来研究与TGFBI相关的生物过程,随后进行了验证。
结果:研究结果表明,TGFBI在肾细胞癌(RCC)组织和细胞中的表达水平均显着升高。此外,siRNA转染细胞中TGFBI的敲除导致RCC细胞增殖的抑制,迁移,侵入性,凋亡,和细胞周期的改变。此外,发现TGFBI阻碍RCC细胞中的上皮-间质转化(EMT)过程。生物信息学分析表明,TGFBI可能通过肿瘤免疫微环境对RCC的各种生物学过程产生影响。此外,我们的研究表明,TGFBI通过激活PI3K/AKT/mTOR/HIF-1α促进RCC进展。
结论:我们的研究表明,TGFBI在RCC中呈现高表达,并通过多种分子机制促进RCC的进展和转移。因此,TGFBI有可能成为未来诊断和治疗RCC的新治疗靶点。
BACKGROUND: Renal cell carcinoma (RCC) is presently recognized as the most prevalent kidney tumor. However, the role and underlying mechanism of action of the conversion factor-inducible protein (
TGFBI), an extracellular matrix protein, in RCC remain poorly understood.
METHODS: In this study, we employed Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry techniques to assess the expression of
TGFBI in RCC tissues or cells. Furthermore, we analyzed the proliferation and migration of RCC cells using CCK8, cloning, scratching, and migration assays. Additionally, we examined apoptosis and cell cycle progression through flow cytometry, analysis. Lastly, we employed gene set enrichment analysis (GSEA) to investigate the biological processes associated with TGFBI, which were subsequently validated.
RESULTS: The findings indicate that
TGFBI exhibits significantly elevated expression levels in both renal cell carcinoma (RCC) tissues and cells. Furthermore, the knockdown of
TGFBI in SiRNA transfected cells resulted in the inhibition of RCC cell proliferation, migration, invasiveness, apoptosis, and alteration of the cell cycle. Additionally, TGFBI was found to impede the epithelial-mesenchymal transition (EMT) process in RCC cells. Bioinformatics analysis suggests that TGFBI may exert its influence on various biological processes in RCC through the tumor immune microenvironment. Moreover, our study demonstrates that
TGFBI promotes RCC progression by activating the PI3K/AKT/mTOR/HIF-1α.
CONCLUSIONS: Our research indicates that TGFBI exhibits high expression in RCC and facilitate RCC progression and metastasis through various molecular mechanisms. Hence, TGFBI has the potential to be a novel therapeutic target for the diagnosis and treatment of RCC in the future.