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Published on: January 31, 2025
CDK5RAP3 Participates in Autophagy Regulation and Is Downregulated in Renal Cancer
1Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Abstract:
Renal cancer is one of the most common malignant urological tumors; however, its diagnosis and treatment are not well established. In the present study, we identified that CDK5 regulatory subunit-associated protein 3 (CDK5RAP3), a putative tumor suppressor in many cancers, was downregulated in renal cancer tissues. Through loss- and gain-of-function experiments, we observed that the action of CDK5RAP3 in renal cancer cells was different in Caki-1 and 769-P cell lines. Knockdown of endogenous CDK5RAP3 in Caki-1 slightly increased cell viability, whereas overexpression of CDK5RAP3 in 769-P cells inhibited cell viability. In addition, we observed that CDK5RAP3 participated in the regulation of autophagy in renal cancer. Knockdown of CDK5RAP3 induced significant inhibition of autophagy in Caki-1 cells but not in 769-P cells. In contrast, overexpression of CDK5RAP3 significantly activated autophagy in 769-P cells, as evidenced by increased LC3-II levels. However, the LC3-II could not be altered by CDK5RAP3 overexpression in Caki-1 cells. These findings demonstrated that CDK5RAP3 is downregulated in renal cancer and may be associated with autophagy.
Insights
CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) is downregulated in renal cancer. This protein influences cell viability and regulates autophagy differently across renal cancer cell lines, suggesting a complex role in kidney cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Renal cancer is a common urological malignancy with challenging diagnosis and treatment.
- CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) is recognized as a potential tumor suppressor in various cancers.
- The specific role of CDK5RAP3 in renal cancer remains underexplored.
Purpose of the Study:
- To investigate the expression levels of CDK5RAP3 in renal cancer tissues.
- To elucidate the functional role of CDK5RAP3 in renal cancer cell lines.
- To determine the association between CDK5RAP3 and autophagy in renal cancer.
Main Methods:
- Analysis of CDK5RAP3 expression in renal cancer tissues.
- Loss-of-function (knockdown) and gain-of-function (overexpression) experiments in Caki-1 and 769-P renal cancer cell lines.
- Assessment of cell viability and autophagy markers (e.g., LC3-II levels).
Main Results:
- CDK5RAP3 was found to be downregulated in renal cancer tissues.
- CDK5RAP3 exhibited differential effects on cell viability in Caki-1 and 769-P cells.
- CDK5RAP3 modulated autophagy differently; knockdown inhibited autophagy in Caki-1, while overexpression activated it in 769-P cells.
Conclusions:
- CDK5RAP3 is downregulated in renal cancer, indicating its potential as a tumor suppressor.
- CDK5RAP3 plays a context-dependent role in regulating renal cancer cell viability.
- CDK5RAP3 is implicated in the regulation of autophagy in renal cancer, with cell-specific effects.
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