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Clear Cell Renal Carcinoma: MicroRNAs With Efficacy in Preclinical In Vivo Models
Ulrich H Weidle1, Adam Nopora1
1Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany adam.nopora@roche.com weidle49@t-online.de.
Abstract:
In order to identify new targets and treatment modalities for clear cell renal carcinoma, we surveyed the literature with respect to microRNAs involved in this disease. In this review, we have focused on up- and down-regulated miRs which mediate efficacy in preclinical clear-cell renal carcinoma-related in vivo models. We have identified 10 up-regulated and 33 down-regulated micro-RNAs according to this criterion. As proof-of-concept, micro-RNAs interfering with VEGF (miR-205p) and mTOR (mir-99a) pathways, which are modulated by approved drugs for this disease, have been identified. miRs targeting hypoxia induced factor-2α (HIF-2α) (miR-145), E3 ubiquitinylases speckle-type POZ protein (SPOP) (miR 520/372/373) and casitas B-lineage lymphoma (CBL) (miR-200a-3p), interfere with druggable targets. Further identified miRs interfere with cell-cycle dependent kinases, such as CDK2 (miR-200c), CDK4, 6 (miR-1) and CDK4, 9 (206c). Transmembrane receptor Ral interacting protein of 76 kD (RLIP76), targeted by mir-137, has emerged as another important target for ccRCC. Additional miRs and their targets merrying further preclinical validation are discussed.
Insights
This review identifies key microRNAs (miRs) regulating clear cell renal carcinoma (ccRCC) in preclinical models. It highlights 10 up-regulated and 33 down-regulated miRs, offering potential new therapeutic targets for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal carcinoma (ccRCC) remains a significant challenge in cancer treatment.
- Identifying novel therapeutic targets and treatment strategies is crucial for improving patient outcomes.
- MicroRNAs (miRs) are increasingly recognized for their roles in cancer development and progression.
Purpose of the Study:
- To conduct a literature review to identify microRNAs (miRs) involved in clear cell renal carcinoma (ccRCC).
- To focus on miRs that show efficacy in preclinical ccRCC in vivo models, highlighting both up- and down-regulated candidates.
- To present potential novel therapeutic targets and treatment modalities for ccRCC based on miR involvement.
Main Methods:
- Systematic literature survey focusing on microRNAs (miRs) in clear cell renal carcinoma (ccRCC).
- Inclusion criteria focused on miRs demonstrating efficacy in preclinical ccRCC in vivo models.
- Identification and categorization of up-regulated and down-regulated miRs and their validated targets.
Main Results:
- Identified 10 up-regulated and 33 down-regulated micro-RNAs (miRs) in preclinical ccRCC models.
- Confirmed miRs targeting key pathways like VEGF (miR-205p) and mTOR (mir-99a).
- Highlighted miRs targeting druggable factors including HIF-2α, SPOP, CBL, and cell-cycle kinases (CDK2, CDK4, 6, 9), and RLIP76.
Conclusions:
- The identified micro-RNAs (miRs) represent promising targets for clear cell renal carcinoma (ccRCC) therapy.
- miRs targeting VEGF, mTOR, HIF-2α, SPOP, CBL, CDKs, and RLIP76 warrant further preclinical investigation.
- This review provides a foundation for developing novel miR-based therapeutic strategies for ccRCC.
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