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

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

doi:10.3389/fonc.2020.00850

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.

Highlights

Colorectal carcinoma (CRC) is the third most common cancer, with 1.8 million newly diagnosed cases and 0.88 million deaths annually [1, 2]
The 60 CRC patients were grouped into circCSPP1high and circCSPP1low groups by the median level of circCSPP1 to investigate the clinical significance of the upregulated expression of circCSPP1 in CRC
The results revealed that circCSPP1 was preferentially located in the cytoplasm of LOVO and HT29 cells (Figure 1F)

Summary

Introduction

Colorectal carcinoma (CRC) is the third most common cancer, with 1.8 million newly diagnosed cases and 0.88 million deaths annually [1, 2]. Exploring the underlying mechanisms of CRC growth and metastasis is crucial to developing more effective treatment options. Accumulating evidence indicates that CRC results from multiple complex factors that include genetic, molecular, and epigenetic alterations [3, 4]. CircCSPP1 Promotes CRC Cells Metastasis interest in cancer research recently [5]. Diverse cellular RNA mechanisms, including protein interactions [6], organization of nuclear architecture [7], regulation of post-translational modifications (PTMs) [8], and protein translation [9], have been the subject of circRNA investigations. CircNSUN2, which can form an RNA–protein ternary complex with IGF2BP2 and HMGA2, promotes CRC liver metastasis by enhancing the RNA stability of HMGA2 [10]

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Conclusion