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Updated: Jun 2, 2026
15:43
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
CDK4 Mediates Cisplatin Resistance in Renal Cell Carcinoma (RCC) Cells by Regulating the ASH1L-CTR1 Axis
Wenjian Zeng1, Xianglong Li2, Hao Cai1
1Department of Oncology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Oncology Research
|June 1, 2026
Summary
Cyclin-dependent kinase 4 (CDK4) drives cisplatin resistance in renal cell carcinoma (RCC) by upregulating ASH1L and downregulating CTR1. Targeting CDK4 or ASH1L can re-sensitize RCC tumors to cisplatin treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cisplatin resistance presents a significant challenge in renal cell carcinoma (RCC) treatment, negatively impacting patient outcomes.
- Understanding the molecular mechanisms underlying cisplatin resistance is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the role and molecular mechanism of cyclin-dependent kinase 4 (CDK4) in the development of cisplatin resistance in RCC.
- To elucidate the downstream targets and pathways regulated by CDK4 in the context of drug resistance.
Main Methods:
- Immunohistochemistry (IHC) to assess CDK4 expression in RCC tissues.
- In vitro studies involving CDK4 overexpression/knockdown in RCC cell lines and drug-resistant sublines.
- In vivo xenograft models to validate CDK4's function.
- Transcriptome sequencing (RNA-seq), CUT&Tag, ChIP, and dual-luciferase reporter assays to determine the molecular mechanism.
Main Results:
- High CDK4 expression in cisplatin-resistant RCC tissues correlated with poor prognosis.
- CDK4 overexpression enhanced cisplatin resistance and malignant phenotypes, while knockdown sensitized cells to cisplatin.
- CDK4 promotes cisplatin resistance by directly upregulating ASH1L (ASH1-Like Histone Lysine Methyltransferase), which in turn inhibits CTR1 (copper transporter 1) expression.
Conclusions:
- The CDK4-ASH1L-CTR1 axis is identified as a critical mediator of cisplatin resistance in renal cell carcinoma.
- Targeting CDK4 or ASH1L offers a potential therapeutic strategy to overcome cisplatin resistance in RCC.
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