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环状CSPP1作为一种竞争性内源RNA，通过上调COL1A1促进结肠癌细胞上皮-间质转化和肝转移。

CircCSPP1 Functions as a ceRNA to Promote Colorectal Carcinoma Cell EMT and Liver Metastasis by Upregulating COL1A1.

作者信息

Wang Qingyuan, Shi Linsen, Shi Kui, Yuan Bo, Cao Gang, Kong Chenchen, Fu Jun, Man Zhongsong, Li Xu, Zhang Xuanfeng, Feng Yifei, Jiang Xinchun, Zhang Xinhui, Yan Jun, Wu Xinyong, Sun Yueming

机构信息

Center of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Xuzhou, China.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Front Oncol. 2020 Jun 16;10:850. doi: 10.3389/fonc.2020.00850. eCollection 2020.

DOI:10.3389/fonc.2020.00850
PMID:32612946
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7308451/
Abstract

The aberrant regulation of circular RNAs (circRNAs), ring structures formed by exon or intron backsplicing, has been identified as a novel characteristic of multiple cancers. However, the role of circRNAs in colorectal carcinoma remains to be elucidated. In the present study, we investigated the mRNA level and the promoting effect of circRNA CSPP1 (circCSPP1) in colorectal carcinoma liver metastasis. By bioinformatic analysis of 10 paired samples of colorectal carcinoma and adjacent mucosal tissues, we identified circCSPP1 as a significantly upregulated circRNA in colorectal carcinoma tissues, and its upregulation was correlated with a higher M stage. The gain- and loss-of-function assays revealed that circCSPP1 promotes the migration and invasion of colorectal carcinoma cells and . Mechanistically, similar miRNA response elements are shared between circCSPP1 and COL1A1. We demonstrated that circCSPP1 upregulates the mRNA levels of COL1A1, which plays a pivotal role in the process of epithelial-mesenchymal transition (EMT), by competitively binding to miR-193a-5p and preventing miR-193a-5p from decreasing the expression of COL1A1. In conclusion, this finding indicates that circCSPP1 may act as a promising therapeutic target by regulating the EMT process in colorectal carcinoma via activation of the circCSPP1/miR-193a-5p/COL1A1 axis.

摘要

环状RNA（circRNAs）是由外显子或内含子反向剪接形成的环状结构，其异常调控已被确定为多种癌症的一个新特征。然而，circRNAs在结直肠癌中的作用仍有待阐明。在本研究中，我们调查了circRNA CSPP1（circCSPP1）在结直肠癌肝转移中的mRNA水平及其促进作用。通过对10对结直肠癌和相邻黏膜组织样本进行生物信息学分析，我们确定circCSPP1是结直肠癌组织中显著上调的circRNA，其上调与更高的M分期相关。功能获得和功能丧失试验表明，circCSPP1促进结直肠癌细胞的迁移和侵袭。机制上，circCSPP1和COL1A1共享相似的miRNA反应元件。我们证明，circCSPP1通过竞争性结合miR-193a-5p并阻止miR-193a-5p降低COL1A1的表达，上调COL1A1的mRNA水平，而COL1A1在上皮-间质转化（EMT）过程中起关键作用。总之，这一发现表明，circCSPP1可能通过激活circCSPP1/miR-193a-5p/COL1A1轴调节结直肠癌的EMT过程，从而成为一个有前景的治疗靶点

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/7308451/76382f70f397/fonc-10-00850-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/7308451/76382f70f397/fonc-10-00850-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/7308451/a151d2a37643/fonc-10-00850-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/7308451/e423f7167321/fonc-10-00850-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/7308451/c377b817d2ea/fonc-10-00850-g0003.jpg
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