Abstract
BackgroundColon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms.MethodsBioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1).ResultsIt was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level.ConclusionTaken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.
Highlights
Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors
CircCSPP1 is highly expressed in colon cancer To explore novel molecular targets for the treatment of colon cancer, the differentially expressed circRNAs between cancer and adjacent normal tissues were first analyzed using two Gene expression omnibus (GEO) datasets (GSE121895 and GSE126094) (Fig. 1A)
CircRNA circularization data indicated that circCSPP1 was spliced by exons 8–11 of the CSPP1 transcript, which was confirmed by Sanger sequencing (Fig. 1F)
Summary
Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. Over the past few decades, the rapid development of molecular biology has enriched the theory of colorectal cancer carcinogenesis [1,2,3,4]. In. Wang et al Journal of Translational Medicine (2022) 20:58 addition, immense progress has been made in diagnostic and treatment strategies for colorectal cancer; the 5-year survival rate of patients with localized disease is 90.1% [5]. Following the metastasis of colorectal cancer to adjacent organs or lymph nodes, the 5-year survival rate of patients decreases to 69.2%. Only 39% of patients with colorectal cancer are diagnosed at the localized stage of the disease, prior to metastasis [6, 7]. Further in-depth investigations of the pathogenesis of colorectal cancer, as well as the identification of more effective early diagnosis and treatment strategies are essential for colorectal cancer
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