miR-507通过靶向STEAP3在肾细胞癌细胞中起抑瘤作用

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2025-01-09 DOI:10.2174/0113862073353340241108053733
Gong Xiaobo, Huang Jian, Guo Linjie, Tang Zhe, Zhong Guangjun, Feng Ye
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引用次数: 0

摘要

导言:近年来,肾细胞癌(RCC)的发病率呈上升趋势,其中转移性 RCC 发病率高,死亡率也很高。虽然人们已认识到微RNA(miRNA)在RCC的发生和发展中起着调控作用,但它们的确切功能、分子机制和潜在的临床意义仍未得到充分阐明。因此,本研究旨在探讨 miR-507 在 RCC 中的作用,并确定 STEAP3 为 miR-507 的下游靶点:方法:采用生物信息学分析方法分析 miR-507 和 STEAP3 在 RCC 标本中的表达。采用 CCK-8、Transwell 和流式细胞术测定评估 miR-507 在 RCC 细胞中的功能。通过荧光素酶报告实验证实了 miR-507 和 STEAP3 之间的联系。免疫印迹法分析了STEAP3、p53和xCT的表达水平:生物信息学分析表明,miR-507在RCC组织中的表达水平较低,且与总生存率低有关。STEAP3在RCC中明显上调。此外,STEAP3被证明是miR-507的靶标。高水平的 miR-507 会降低 STEAP3 的表达,导致细胞活力、凋亡和迁移能力停滞不前。而敲除 miR-507 则可逆转这种趋势。研究还发现,miR-507通过op53/xCT途径发挥抑制作用:结论:在 RCC 中,miR-507 可调节 SETAP3/p53/xCT 轴的表达,表现出抑制肿瘤的作用。这些发现为监测和治疗 RCC 提供了前瞻性的生物标志物。
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miR-507 Acts as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting STEAP3.

Introduction: In recent years, there has been a rise in the incidence of renal cell carcinoma (RCC), with metastatic RCC being a prevalent and significant contributor to mortality. While a regulatory role for microRNAs (miRNAs) in the development and progression of RCC has been recognized, their precise functions, molecular mechanisms, and potential clinical implications remain inadequately elucidated. Hence, this study aimed to explore the role of miR-507 in RCC and identify STEAP3 as a downstream target of miR-507.

Methods: Bioinformatics analysis was used to analyze the expression of miR-507 and STEAP3 in RCC specimens. CCK-8, Transwell, and flow cytometry assays were used to assess the function of miR-507 in RCC cells. The connection between miR-507 and STEAP3 was confirmed through a luciferase reporter assay. The expression level of STEAP3, p53, and xCT was analyzed by western blotting.

Results: Bioinformatics analysis showed that miR-507 was expressed at low levels in RCC tissues and was linked to poor overall survival. STEAP3 was found to be significantly upregulated in RCC. Further, STEAP3 was shown to be targeted by miR-507. High levels of miR-507 reduced the expression of STEAP3, leading to stagnant cell viability, apoptosis, and migrative capacity. Whereas miR-507 knockdown reverted such a tendency. The study also discovered that miR-507 exerted its inhibitory effect through the op53/xCT pathway.

Conclusion: Within RCC, miR-507 modulates the expression of SETAP3/p53/xCT axis, exhibiting a tumor suppressive effect. These discoveries offer present prospective biomarkers for both surveillance and treatment of RCC.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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