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

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

doi:10.3389/fonc.2020.00850

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

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

Authors

Qingyuan Wang^{1

2}, Linsen Shi³, Kui Shi¹, Bo Yuan¹, Gang Cao¹, Chenchen Kong¹, Jun Fu¹, Zhongsong Man¹, Xu Li¹, Xuanfeng Zhang¹, Yifei Feng², Xinchun Jiang¹, Xinhui Zhang¹, Jun Yan⁴, Xinyong Wu⁵, Yueming Sun²

Affiliations

¹ Center of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Xuzhou, China.
² Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Department of Gastrointestinal Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁴ Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, Beijing, China.
⁵ Department of General Surgery, Xuzhou Central Hospital, Xuzhou, China.

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 in vitro and in vivo. 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.

Keywords: COL1A1; CeRNA; EMT; circRNA; metastasis.