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作为透明细胞肾细胞癌的一种潜在预后生物标志物。

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

作者信息

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

机构信息

Graduate School of the First Clinical Medical College of Jinan University, Guangzhou, China.

Department of Urology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

出版信息

Transl Cancer Res. 2025 Feb 28;14(2):1246-1264. doi: 10.21037/tcr-24-1397. Epub 2025 Feb 26.

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 (), a subunit of mitochondrial ATP synthase, is integral to the energy metabolism of specific tumors. While prior research has established a link between 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. expression in ccRCC was validated using the Human Protein Atlas database. The role of in ccRCC was further characterized through a series of assays, including wound healing, transwell invasion, cell counting kit-8 proliferation, and flow cytometry.

RESULTS

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 expression. An inverse relationship was observed between expression and both the clinical stage and histological grade of ccRCC, yet it is positively associated with improved prognosis. Silencing expression enhanced the malignant biological properties of ccRCC, while its upregulation inhibited these effects. Furthermore, knockdown activated the Wnt/β-catenin signaling pathway, whereas its overexpression resulted in pathway suppression.

CONCLUSIONS

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

摘要

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,其临床特点是治疗周期长且治疗效果欠佳。三磷酸腺苷(ATP)合酶F1亚基α(ATP5A1)是线粒体ATP合酶的一个亚基,对特定肿瘤的能量代谢至关重要。虽然先前的研究已证实ATP5A1表达与恶性肿瘤之间存在联系,但其在ccRCC中的具体功能和临床意义尚待阐明。本研究旨在探讨ATP5A1在ccRCC中的作用,并探究其潜在的分子机制。

方法

通过癌症基因组图谱分析ccRCC及其相应癌旁组织的RNA测序数据,以评估其诊断和预后意义。使用人类蛋白质图谱数据库验证ccRCC中ATP5A1的表达。通过一系列实验进一步明确ATP5A1在ccRCC中的作用,包括伤口愈合实验、Transwell侵袭实验、细胞计数试剂盒-8增殖实验和流式细胞术。

结果

ATP5A1表达水平在17种肿瘤类型中升高,而在包括ccRCC、食管癌和结肠腺癌在内的其他15种肿瘤类型中显著下调。与293细胞和正常肾组织相比,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表达增强了ccRCC的恶性生物学特性,而其过表达则抑制了这些效应。此外,敲低ATP5A1激活了Wnt/β-连环蛋白信号通路,而过表达则导致该信号通路受到抑制。

结论

总体而言,本研究表明ATP5A1可能作为ccRCC诊断、预后评估及治疗靶点的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fab/11912089/1234bb8c17fc/tcr-14-02-1246-f1.jpg

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