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环状 RNA PRRC2A 通过上皮-间充质转化促进血管生成和转移,并上调肾细胞癌中的 TRPM3。

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

机构信息

Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, P. R. China.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

出版信息

Theranostics. 2020 Mar 15;10(10):4395-4409. doi: 10.7150/thno.43239. eCollection 2020.

Abstract

: 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. : 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. : circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both and . 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. : These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.

摘要

环状 RNA(circRNAs)已被鉴定为多种癌症中必不可少的调节因子。然而,circRNAs 在肾细胞癌(RCC)中的作用机制仍知之甚少。

在本研究中,我们旨在鉴定新的circRNAs 来调节 RCC 上皮-间充质转化(EMT),并随后确定它们的调节机制和临床意义。

circPRRC2A 通过 circRNA 微阵列鉴定,并通过 qRT-PCR 验证。通过 和 评估 circPRRC2A 在 RCC 转移中的作用。我们发现,circPRRC2A 的表达增加与 RCC 患者的晚期临床分期和较差的生存相关。从机制上讲,我们的结果表明,circPRRC2A 通过海绵 miR-514a-5p 和 miR-6776-5p 来防止组织特异性癌基因 TRPM3mRNA 的降解。此外,circPRRC2A 促进了 RCC 患者的肿瘤 EMT 和侵袭性。

这些发现暗示了一个令人兴奋的可能性,即 circPRRC2A 可能被用作 RCC 患者的治疗和预后靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0a1/7150475/add27f955cb5/thnov10p4395g001.jpg

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