DLX5 Promotes Radioresistance in Renal Cell Carcinoma by Upregulating c-Myc Expression.

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Danfei Hu, Mingyao Li, Xiaodong Chen
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Abstract

Background: Renal cell carcinoma (RCC) is a prevalent and aggressive kidney cancer with notable metastatic potential. While radiotherapy is effective for treating metastatic RCC, the emergence of radioresistance presents a major challenge. This study explores the role of DLX5, previously identified as an oncogene in various cancers, in the development of radioresistance in RCC.

Methods: Distal-less homeobox 5 (DLX5) expression was measured using western blot analysis. To study the effects of DLX5, its expression was knocked down in 786-O and Caki-1 RCC cell lines through si-DLX5 transfection, and the impact of DLX5 on RCC cell proliferation and radioresistance was assessed using cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay, flow cytometry, colony formation, immunofluorescence, and western blot assays. The underlying mechanisms were explored through western blot, colony formation, and CCK-8 assays. In vivo effects were examined using a xenograft mouse model.

Results: In silico results showed increased DLX5 levels in RCC tissues. Similarly, DLX5 expression was elevated in RCC cell lines. Silencing DLX5 reduced RCC cell proliferation and induced apoptosis in vitro. Additionally, DLX5 knockdown decreased radioresistance and increased DNA damage in RCC cells. Mechanistic studies revealed that DLX5 promotes radioresistance through the upregulation of c-Myc. In vivo, DLX5 silencing impeded tumor growth and reduced radioresistance.

Conclusion: DLX5 contributes to RCC cell growth and radioresistance by upregulating c-Myc expression, highlighting its potential as a target for overcoming radioresistance in RCC.

DLX5通过上调c-Myc表达促进肾细胞癌放射耐药。
背景:肾细胞癌(RCC)是一种常见的侵袭性肾癌,具有明显的转移潜力。虽然放疗对治疗转移性肾细胞癌是有效的,但放射耐药的出现提出了一个主要挑战。本研究探讨了DLX5在RCC放射耐药发展中的作用,DLX5先前被确定为多种癌症的致癌基因。方法:采用western blot法检测无远端同源盒5 (DLX5)的表达。为了研究DLX5的作用,通过si-DLX5转染786-O和Caki-1 RCC细胞株,降低DLX5的表达,并通过细胞计数试剂盒-8 (CCK-8)、5-乙基-2′-脱氧尿苷(EdU)结合实验、流式细胞术、集落形成、免疫荧光和western blot检测DLX5对RCC细胞增殖和辐射抗性的影响。通过western blot、菌落形成和CCK-8检测来探索其潜在机制。使用异种移植小鼠模型检测体内效应。结果:计算机成像结果显示RCC组织中DLX5水平升高。同样,DLX5在RCC细胞系中表达升高。沉默DLX5可降低RCC细胞增殖,诱导细胞凋亡。此外,DLX5敲除降低了RCC细胞的辐射抗性并增加了DNA损伤。机制研究表明DLX5通过上调c-Myc促进辐射抗性。在体内,DLX5沉默抑制肿瘤生长并降低放射耐药。结论:DLX5通过上调c-Myc的表达,促进了RCC细胞的生长和放射耐药,突出了其作为克服RCC放射耐药靶点的潜力。
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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