Dataset Information

CircPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma.

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.

SUBMITTER: Li W

PROVIDER: S-EPMC7150475 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Li Wei W Yang Feng-Qiang FQ Sun Chen-Min CM Huang Jian-Hua JH Zhang Hai-Min HM Li Xue X Wang Guang-Chun GC Zhang Ning N Che Jian-Ping JP Zhang Wen-Tao WT Yan Yang Y Yao Xu-Dong XD Peng Bo B Zheng Jun-Hua JH Liu Min M

Theranostics 20200315 10

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 v ...[more]

PMID: 32292503

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Project description:BACKGROUND:Metastasis is the principal cause of renal cell carcinoma-associated mortality. Metadherin (MTDH) was identified as a vital metastasis driver involved in the metastatic progression of various types of tumors, suggesting that MTDH is a prognostic metastatic biomarker and potential therapeutic target. The role and mechanism of MTDH in the metastatic progression of ccRCC have not yet been adequately explored. RESULTS:MTDH was remarkably elevated in ccRCC tissues, especially in metastatic ccRCC tissues, compared with normal kidney tissues and correlated with advanced clinicopathological features and poor prognosis. MTDH activated ERK signaling and EMT, thus promoting the migration and invasion of ccRCC cells. The interaction between MTDH and SND1 at the protein level was confirmed using immunoprecipitation and immunofluorescence. Based on the analysis of datasets from GEO and TCGA, SND1 was remarkably increased in ccRCC, especially in metastatic ccRCC, and associated with advanced clinicopathological features and poor prognosis. Knockdown of SND1 mainly abolished the migration and invasion of ccRCC cells by blocking MTDH-mediated ERK and EMT signaling activation. CONCLUSION:These results revealed that MTDH may be a prognostic metastatic biomarker of ccRCC that promotes ccRCC metastasis by activating SND1-mediated the ERK and EMT signaling pathways. MTDH may serve as an anti-tumor therapeutic target that can be applied for the clinical treatment of metastatic ccRCC. METHODS:MTDH/SND1 mRNA expression in clear cell renal cell carcinoma (ccRCC) was comprehensively estimated by analysis of GEO-ccRCC and TCGA-KIRC datasets with R software and packages. MTDH protein expression was assessed in a total of 111 ccRCC patients from Peking University First Hospital by immunohistochemistry (IHC). In vitro migration and invasion assays were carried out, and an in vivo metastatic mouse model was developed to investigate the biological functions of MTDH in ccRCC cells. Correlation analysis, immunoprecipitation, western blotting and immunofluorescence were applied to explore the molecular mechanisms of MTDH in ccRCC.

Dataset Information

CircPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma.

Publications

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

Similar Datasets

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