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Published on: March 27, 2020
piR-RCC Suppresses Renal Cell Carcinoma Progression by Facilitating YBX-1 Cytoplasm Localization
Ruyue Wang1, Fan Li1, Yudong Lin1
1Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
Abstract:
PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, are widely expressed in eukaryotes and deregulated in several pathologies, including cancer. Little is known about their function and mechanism in renal cell carcinoma (RCC) progression. Herein, a down-regulated piRNA in RCC, termed piR-hsa-28489 (designated as piR-RCC), is identified to impede RCC progression both in vivo and in vitro. Mechanistically, piR-RCC directly interacts with Y-box binding protein 1 (YBX-1), thus impeding p-AKT-mediated YBX-1 phosphorylation and its subsequent nuclear translocation. Moreover, YBX-1 coordinates the transcription of ETS homologous factor (EHF) as a repressor factor. Consequently, piR-RCC enhances EHF expression, leading to the inhibition of RCC proliferation and metastasis. Based on these, a biomimetic nanoparticle platform is constructed to achieve RCC-specific targeted delivery of piR-RCC. The nanoparticles are fabricated using a cell membrane coating derived from cancer cells and used to encapsulate and deliver piR-RCC plasmids to renal orthotopic implantation in mice, hindering RCC progression. This study illustrates piR-RCC/YBX-1/EHF signaling axis in RCC, offering a promising therapeutic avenue for RCC.
Insights
A novel PIWI-interacting RNA (piRNA), piR-RCC, inhibits renal cell carcinoma (RCC) progression by targeting the YBX-1/EHF pathway. Biomimetic nanoparticles deliver piR-RCC, offering a potential new therapy for RCC.
Area of Science:
- Molecular Biology
- Oncology
- Biotechnology
Background:
- PIWI-interacting RNAs (piRNAs) are small non-coding RNAs implicated in various pathologies, including cancer.
- The specific role of piRNAs in renal cell carcinoma (RCC) progression remains largely uncharacterized.
Purpose of the Study:
- To investigate the function and mechanism of piRNAs in RCC progression.
- To identify a novel piRNA that can impede RCC development.
- To develop a targeted delivery system for potential therapeutic applications.
Main Methods:
- Identification and characterization of a down-regulated piRNA (piR-RCC) in RCC.
- In vitro and in vivo studies to assess piR-RCC's effect on RCC progression.
- Investigation of the molecular mechanism involving Y-box binding protein 1 (YBX-1) and ETS homologous factor (EHF).
- Construction and evaluation of a biomimetic nanoparticle platform for targeted piR-RCC delivery.
Main Results:
- piR-RCC was found to be down-regulated in RCC and inhibits RCC progression.
- piR-RCC directly interacts with YBX-1, preventing its phosphorylation and nuclear translocation.
- This interaction leads to enhanced EHF expression, suppressing RCC proliferation and metastasis.
- Biomimetic nanoparticles successfully delivered piR-RCC to renal tumors in mice, inhibiting RCC progression.
Conclusions:
- The piR-RCC/YBX-1/EHF signaling axis plays a critical role in inhibiting RCC progression.
- piR-RCC represents a potential therapeutic target for renal cell carcinoma.
- Biomimetic nanoparticle delivery of piR-RCC offers a promising strategy for RCC treatment.
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