Journal
THERANOSTICS
Volume 10, Issue 10, Pages 4395-4409Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.43239
Keywords
circular RNA; RCC; circPRRC2A; lung metastasis; therapeutic target
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Funding
- National Natural Science Foundation of China [81602469, 81502426]
- Fundamental Research Funds for the Central Universities [2016KJ045]
- Foundation of Tongren Xinxing [2019shtrxx07]
- Joint Medical Research Program of Shanghai Changning District Science and Technology Commission [CNKW2018Y03, CNKW2018Y05]
- Research Project Funding of Shanghai Health and Family Planning Commission [20164Y0093]
- Zhejiang Health Young Talents Project [2019336921]
- Zhejiang Innovative Talents Project [2020392710]
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Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.
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