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

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.