CircCSNK1G3 up-regulates miR-181b to promote growth and metastasis via TIMP3-mediated epithelial to mesenchymal transitions in renal cell carcinoma

CircCSNK1G3 上调 miR-181b,通过 TIMP3 介导的肾细胞癌上皮-间质转化促进生长和转移

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作者:Wen Li, Yang-Yi-Yan Song, Ting Rao, Wei-Min Yu, Yuan Ruan, Jin-Zhuo Ning, Xiao-Bing Yao, Song-Yi-Sha Yang, Fan Cheng

Abstract

Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation.

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