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KCNJ2促进肾透明细胞癌进展及葡萄糖代谢。

KCNJ2 Facilitates Clear Cell Renal Cell Carcinoma Progression and Glucose Metabolism.

作者信息

Zhao Qiyue, Wei Zhengshu, Yang Guanglin, Wei Liwei, Chen Hao, Cui Zelin, Liao Naikai, Qin Min, Cheng Jiwen

机构信息

Department of Urology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Department of Surgery, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

出版信息

Int J Genomics. 2025 Apr 24;2025:2210652. doi: 10.1155/ijog/2210652. eCollection 2025.

DOI:10.1155/ijog/2210652
PMID:40314029
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12045686/
Abstract

Clear cell renal cell carcinoma (ccRCC) is marked by aggressive characteristics and a poor prognosis. The involvement of KCNJ2, an inward rectifying potassium channel, in the progression of ccRCC, along with its potential roles in immune modulation and metabolic pathways, remains unclear. The Cancer Genome Atlas (TCGA) database was utilized to analyze the gene expression, clinicopathological characteristics, and clinical relevance of KCNJ2. The prognostic value of KCNJ2 in ccRCC was evaluated with Kaplan-Meier survival analysis and receiver operating characteristic curve analyses. The TCGA-KIRC dataset was utilized to analyze tumor microenvironment (TME), focusing on tumor-infiltrating immune cells and immunomodulators. The biological functions of KCNJ2 were investigated in vitro using CCK-8, flow cytometry, wound healing, transwell, qRT-PCR, and Western blotting assays. KCNJ2 expression was notably higher in ccRCC than in normal kidney tissues, with increased levels associated with advanced tumor stages. However, KCNJ2 did not exhibit obvious prognostic value. Coexpression analysis identified associations with genes implicated in energy metabolism. Analysis of the TME and immune profile indicated a link between KCNJ2 expression and immune cell infiltration, along with particular immune checkpoints. studies demonstrated that KCNJ2 overexpression enhanced cell proliferation, migration, invasion, glucose production, and ATP generation. KCNJ2 plays a crucial role in ccRCC progression through affecting glucose metabolism and immune responses. Our findings reveal the functional role of KCNJ2 in promoting tumor progression and metabolic reprogramming in ccRCC, highlighting its therapeutic potential as a novel target for ccRCC treatment. Further studies are essential to clarify the mechanisms by which KCNJ2 affects ccRCC biology and to evaluate its clinical relevance.

摘要

透明细胞肾细胞癌(ccRCC)具有侵袭性特征且预后较差。内向整流钾通道KCNJ2在ccRCC进展中的作用,以及其在免疫调节和代谢途径中的潜在作用仍不清楚。利用癌症基因组图谱(TCGA)数据库分析KCNJ2的基因表达、临床病理特征及临床相关性。采用Kaplan-Meier生存分析和受试者工作特征曲线分析评估KCNJ2在ccRCC中的预后价值。利用TCGA-KIRC数据集分析肿瘤微环境(TME),重点关注肿瘤浸润免疫细胞和免疫调节因子。使用CCK-8、流式细胞术、伤口愈合实验、Transwell实验、qRT-PCR和蛋白质免疫印迹法在体外研究KCNJ2的生物学功能。KCNJ2在ccRCC中的表达明显高于正常肾组织,其水平升高与肿瘤晚期相关。然而,KCNJ2未表现出明显的预后价值。共表达分析确定了与能量代谢相关基因的关联。TME和免疫图谱分析表明KCNJ2表达与免疫细胞浸润以及特定免疫检查点之间存在联系。研究表明,KCNJ2过表达增强了细胞增殖、迁移、侵袭、葡萄糖生成和ATP产生。KCNJ2通过影响葡萄糖代谢和免疫反应在ccRCC进展中起关键作用。我们的研究结果揭示了KCNJ2在促进ccRCC肿瘤进展和代谢重编程中的功能作用,突出了其作为ccRCC治疗新靶点的治疗潜力。进一步的研究对于阐明KCNJ2影响ccRCC生物学的机制以及评估其临床相关性至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/12b774637312/IJG2025-2210652.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/64b911954f2a/IJG2025-2210652.002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/12b774637312/IJG2025-2210652.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/64b911954f2a/IJG2025-2210652.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/2657a3239795/IJG2025-2210652.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/da16d327e3c9/IJG2025-2210652.004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a741/12045686/12b774637312/IJG2025-2210652.006.jpg

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本文引用的文献

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Glucose-1,6-bisphosphate: A new gatekeeper of cerebral mitochondrial pyruvate uptake.葡萄糖-1,6-二磷酸:脑线粒体丙酮酸摄取的新守门员。
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Renal cell carcinoma.肾细胞癌。
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KCNJ2/HIF1α positive-feedback loop promotes the metastasis of osteosarcoma.KCNJ2/HIF1α 正反馈环促进骨肉瘤的转移。
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