Normal kidney tissue derived extracellular vesicles suppress clear cell renal cell carcinoma progression via transfer their inhibitory miRNAs
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Updated: Jun 3, 2026
An Enrichment Method for Small Extracellular Vesicles Derived from Liver Cancer Tissue
Published on: February 3, 2023
Liqun Huang1, Huaru Zhang2, Zhiguo Chen3
1Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, PR China; Department of Urology, Shanghai Geriatric Medical Center, Zhongshan Hospital Fudan University Minhang Campus, Shanghai, 201104, PR China.
Abstract:
Tumor-derived extracellular vesicles (EVs) contribute to tumor progression and metastasis. We recently reported that EVs derived from normal kidney tissues (N-EVs) suppress sterile cardiac inflammation in myocardial ischemic injury models. However, whether N-EVs affect the progression of renal cancer remains elusive. In the present study, we demonstrated that N-EVs inhibit the proliferation and invasion of clear cell renal cell carcinoma (ccRCC) in vitro. When administered intravenously, N-EVs were mainly retained within the tumors and suppressed ccRCC progression in cancer-bearing murine models. Further miRNA sequencing revealed that the target genes of the top 20 miRNAs in N-EVs were primarily enriched in signaling pathways, including the MAPK and Ras pathways. Moreover, N-EVs treatment modulated the tumor microenvironment and inhibited cancer cell proliferation and angiogenesis through the transfer of their inhibitory miRNAs. Therefore, manipulating normal tissue-derived EVs (including those from cultured kidney organoids) or their miRNA cargo may represent a promising potential strategy for treating ccRCC in clinical settings.
Insights
Normal kidney extracellular vesicles (N-EVs) inhibit clear cell renal cell carcinoma (ccRCC) progression by transferring inhibitory miRNAs. This suggests N-EVs as a potential therapeutic strategy for ccRCC treatment.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Tumor-derived extracellular vesicles (EVs) promote cancer progression and metastasis.
- Normal tissue-derived EVs (N-EVs) have shown therapeutic potential in other conditions.
- The role of N-EVs in renal cancer progression was previously unknown.
Purpose of the Study:
- To investigate the effect of N-EVs on clear cell renal cell carcinoma (ccRCC) progression.
- To explore the underlying mechanisms of N-EVs' action in ccRCC.
Main Methods:
- In vitro experiments assessing ccRCC cell proliferation and invasion.
- In vivo studies using murine ccRCC models with intravenous N-EVs administration.
- miRNA sequencing of N-EVs and analysis of target gene enrichment in signaling pathways.
Main Results:
- N-EVs significantly inhibited ccRCC cell proliferation and invasion in vitro.
- Intravenously administered N-EVs were retained in ccRCC tumors and suppressed tumor progression in vivo.
- N-EVs contain specific miRNAs that target key signaling pathways like MAPK and Ras.
- N-EVs modulated the tumor microenvironment, inhibiting proliferation and angiogenesis via miRNA transfer.
Conclusions:
- N-EVs exhibit anti-cancer properties against ccRCC.
- N-EVs exert their effects by transferring inhibitory miRNAs that modulate tumor signaling and microenvironment.
- Targeting N-EVs or their miRNA cargo presents a promising therapeutic avenue for ccRCC treatment.
