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COL1A1通过PI3K/Akt途径调节上皮-间质转化,从而驱动肾透明细胞癌的肿瘤进展。

COL1A1 drives tumor progression in kidney renal clear cell carcinoma by regulating EMT through the PI3K/Akt pathway.

作者信息

Zhao Hainan, Wang Ermin

机构信息

Nephrology department, The First Affiliated Hospital of Jinzhou Medical University, Renmin Street, Jinzhou, 121000, Liaoning, China.

出版信息

Cancer Cell Int. 2025 Aug 25;25(1):314. doi: 10.1186/s12935-025-03956-y.

Abstract

The aggressiveness of clear cell renal cell carcinoma (KIRC) plays a crucial role in patient prognosis. This study investigated the role of COL1A1 in KIRC progression and its underlying molecular mechanisms through bioinformatics analysis, in vitro experiments, and xenograft mouse models. COL1A1 expression was significantly upregulated in KIRC and correlated with poor patient outcomes. Knockdown of COL1A1 inhibited tumor cell proliferation, migration, and invasion in both in vitro and xenograft models, as well as suppression of epithelial-mesenchymal transition (EMT). Knockdown of COL1A1 also significantly reduced the protein levels of the stemness markers OCT4 and SOX2 in KIRC cells. Additionally, COL1A1 inhibition impaired activation of the PI3K/Akt signaling pathway. These findings underscore the pivotal role of the COL1A1/PI3K/Akt axis in KIRC progression and suggest potential therapeutic strategies targeting this pathway.

摘要

透明细胞肾细胞癌(KIRC)的侵袭性在患者预后中起着关键作用。本研究通过生物信息学分析、体外实验和异种移植小鼠模型,探讨了COL1A1在KIRC进展中的作用及其潜在分子机制。COL1A1在KIRC中表达显著上调,且与患者不良预后相关。在体外和异种移植模型中,敲低COL1A1均抑制肿瘤细胞增殖、迁移和侵袭,并抑制上皮-间质转化(EMT)。敲低COL1A1还显著降低了KIRC细胞中干性标志物OCT4和SOX2的蛋白水平。此外,COL1A1抑制削弱了PI3K/Akt信号通路的激活。这些发现强调了COL1A1/PI3K/Akt轴在KIRC进展中的关键作用,并提示了针对该通路的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5505/12376327/1a31c191c75b/12935_2025_3956_Fig1_HTML.jpg

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