| Objective Colorectal cancer(CRC)is one of the most common malignancies in the world,with the third highest incidence and the second highest mortality rate in the world,and the incidence of CRC is currently increasing globally and is trending younger.Studies have shown that CRC may be caused by multiple factors,but there is still a lack of specific indicators for the diagnosis of early colorectal cancer,which issues a challenge for the prevention and treatment of colorectal cancer in clinical.CircRNAs are a special class of non-coding RNA molecules formed by the 3’to5’end loops of RNAs,which are highly expressed in the eukaryotic transcriptomeand have a highly stable covalently closed loop structure without the 5’cap structure and 3’multimeric tail.Initially,circRNAs was mainly considered as a"byproduct"of aberrant splicing.It has been reported that circRNAs play a pro-or anti-cancer role in the development of malignant tumors such as liver and gastric cancers.However,studies on the mechanism of circRNAs in colorectal carcinogenesis and development are still rare,and this study was devoted to investigate the role of circRNAs in colorectal carcinogenesis and development,in order to provide some references for further research on the pathogenesis of colorectal cancer and clinical treatment.Methods The differentially expressed circRNA,miRNA and mRNA were screened from GEO database using bioinformatics,and the binding relationship between circRNA and miRNA was predicted by CSCD,Circular RNA Interactome database and Human circRNA Database.Target Scan and miRTar Base websites were used to predict the target genes of miRNAs,and finally the regulatory network of circRNA-miRNA-mRNA was established based on the theoretical basis of ceRNA,and the pathway enrichment analysis of target genes was performed.The expression differences of hsa＿circ＿0040809,miR-375,and CLDN1 in the tissue samples of colorectal cancer patients collected clinically were detected by qRT-PCR,and the correlation between hsa＿circ＿0040809 and the survival prognosis and clinical characteristics of patients was analyzed.Finally,the effects of hsa＿circ＿0040809 on the proliferation function of colorectal cancer cells were detected by CCK-8,clone formation assay and Ed U assay,the effects of hsa＿circ＿0040809 on the migration function of intestinal cancer cells were detected by scratch and transwell assay,and the effects of hsa＿circ＿0040809 on the the effect of cell cycle.Results 1.Based on the sequencing dataset in GEO database,we compared the tumor group with the control group,and finally screened the differentially expressed circRNA,miRNA and mRNA,and successfully constructed the CRC-related hsa＿circ＿0040809-miR-375-CLDN1 regulatory network.2.Hsa＿circ＿0040809 is highly expressed in colorectal cancer and can significantly promote the proliferation and migration ability of colorectal cancer cells and affect the cell cycle.By knocking down the expression of hsa＿circ＿0040809,the migration and proliferation ability of colorectal cancer cells will be inhibited and the S phase of cell cycle will be shortened.3.Univariate and multivariate analysis suggested that survival of colorectal cancer patients was correlated with T-stage and hsa＿circ＿0040809 expression level(P<0.05).4.miR-375 is a target miRNA for has＿circ＿0040809,and is lowly expressed in colorectal cancer.5.CLDN1 was highly expressed in colorectal cancer and was enriched in WNT BETA CATENIN pathway.Conclusion1.The expression of circRNA has＿circ＿0040809 was significantly increased in colorectal cancer.2.Knockdown of hsa＿circ＿0040809 suppressed the proliferation and migration ability of colorectal cancer cells and shortened S phase in the cell cycle.3.High expression of cirrna has＿circ＿0040809 in colorectal cancer is associated with poor prognosis of colorectal cancer.4.Hsa＿circ＿0040809 can promote the development of colorectal cancer by adsorbing miR-375 and thus promoting the expression of miR-375 target gene CLDN1. |
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