ATP5A1 as a potential prognostic biomarker in clear-cell renal cell carcinoma.

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2025-02-28 Epub Date: 2025-02-26 DOI:10.21037/tcr-24-1397

Wei Zhou, Qianli Tang, Jun Wu, Minyu Huang, Qun Huang, Tianzi Qin, Ning Tang, Shasha Gai

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引用次数: 0

Abstract

Background: Clear cell renal cell carcinoma (ccRCC), a malignant neoplasm originating in the renal tubules, is characterized by extended treatment durations and suboptimal therapeutic outcomes in clinical settings. Adenosine triphosphate (ATP) synthase F1 subunit α (ATP5A1), a subunit of mitochondrial ATP synthase, is integral to the energy metabolism of specific tumors. While prior research has established a link between ATP5A1 expression and malignancies, its precise function and clinical significance in ccRCC are yet to be elucidated. The study aims to investigate the role of ATP5A1 in ccRCC and to explore the underlying molecular mechanisms.

Methods: The RNA sequencing data from ccRCC and corresponding adjacent tissues were analyzed through The Cancer Genome Atlas to evaluate their diagnostic and prognostic implications. ATP5A1 expression in ccRCC was validated using the Human Protein Atlas database. The role of ATP5A1 in ccRCC was further characterized through a series of assays, including wound healing, transwell invasion, cell counting kit-8 proliferation, and flow cytometry.

Results: ATP5A1 expression levels were elevated across 17 tumor types while being notably downregulated in 15 others, including ccRCC, esophageal carcinoma, and colon adenocarcinoma. Compared to 293 cells and adjacent normal kidney tissues, renal cancer cells and tissues exhibited a significant reduction in ATP5A1 expression. An inverse relationship was observed between ATP5A1 expression and both the clinical stage and histological grade of ccRCC, yet it is positively associated with improved prognosis. Silencing ATP5A1 expression enhanced the malignant biological properties of ccRCC, while its upregulation inhibited these effects. Furthermore, ATP5A1 knockdown activated the Wnt/β-catenin signaling pathway, whereas its overexpression resulted in pathway suppression.

Conclusions: Collectively, this study indicates that ATP5A1 may serve as a potential biomarker for the diagnosis, prognosis, and therapeutic targeting of ccRCC.

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ATP5A1作为透明细胞肾细胞癌的潜在预后生物标志物。

背景：透明细胞肾细胞癌（ccRCC）是一种起源于肾小管的恶性肿瘤，其特点是治疗时间长，临床治疗效果不理想。三磷酸腺苷（ATP）合成酶F1亚基α (ATP5A1)是线粒体ATP合成酶的一个亚基，在特定肿瘤的能量代谢中是不可或缺的。虽然先前的研究已经建立了ATP5A1表达与恶性肿瘤之间的联系，但其在ccRCC中的确切功能和临床意义尚未阐明。本研究旨在探讨ATP5A1在ccRCC中的作用，并探讨其潜在的分子机制。方法：通过The Cancer Genome Atlas对ccRCC及相应癌旁组织的RNA测序数据进行分析，评估其诊断和预后意义。使用Human Protein Atlas数据库验证ATP5A1在ccRCC中的表达。ATP5A1在ccRCC中的作用通过一系列实验进一步表征，包括伤口愈合、transwell侵袭、细胞计数试剂盒-8增殖和流式细胞术。结果：ATP5A1表达水平在17种肿瘤类型中升高，而在其他15种肿瘤类型中显著下调，包括ccRCC、食管癌和结肠腺癌。与293细胞和邻近正常肾组织相比，肾癌细胞和组织中ATP5A1的表达明显降低。ATP5A1表达与ccRCC的临床分期和组织学分级呈负相关，但与预后改善呈正相关。沉默ATP5A1表达可增强ccRCC的恶性生物学特性，而上调ATP5A1表达可抑制这些作用。此外，ATP5A1敲低激活了Wnt/β-catenin信号通路，而其过表达导致通路抑制。结论：总的来说，本研究表明ATP5A1可能作为ccRCC的诊断、预后和治疗靶向的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.