Theranostics 2020; 10(10):4395-4409. doi:10.7150/thno.43239

Research Paper

circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma

Wei Li1,2*, Feng-Qiang Yang3,1*, Chen-Min Sun4*, Jian-Hua Huang1*, Hai-Min Zhang1, Xue Li5, Guang-Chun Wang1, Ning Zhang2, Jian-Ping Che1, Wen-Tao Zhang1, Yang Yan1, Xu-Dong Yao1✉, Bo Peng1, Jun-Hua Zheng6✉, Min Liu7✉

1. Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, P. R. China.
2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
3. Department of Urology, Ninghai Hospital, Branch of Shanghai Tenth People's Hospital, Zhejiang, P. R. China.
4. Department of Anesthesiology, Tongren Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
5. Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P. R. China.
6. Department of Urology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
7. Department of Urology, Tongren Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
*These authors contributed equally to this work.

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Citation:
Li W, Yang FQ, Sun CM, Huang JH, Zhang HM, Li X, Wang GC, Zhang N, Che JP, Zhang WT, Yan Y, Yao XD, Peng B, Zheng JH, Liu M. circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma. Theranostics 2020; 10(10):4395-4409. doi:10.7150/thno.43239. Available from http://www.thno.org/v10p4395.htm

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Abstract

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.

Keywords: circular RNA, RCC, circPRRC2A, lung metastasis, therapeutic target