Objective To investigate the expression and clinical relevance of Connexin 43(CX43)in colorectal cancer,as well as its role and mechanisms in colorectal cancer.Methods The expression of GJA1 in colorectal cancer and its association with clinical characteristics of colorectal cancer were analyzed on online websites.The transcriptomic data of colorectal cancer from the TCGA database was downloaded,and bioinformatics methods were utilized to analyze the expression of GJA1 in paired colorectal cancer.Clinical colorectal cancer samples were collected for validation of CX43 expression through qPCR,Western blotting,and immunohistochemistry techniques.Transcriptional profiling was performed by overexpressing GJA1 in HCT116 cells to explore its role and mechanisms in colorectal cancer.The proliferative capacity of HCT116 and LOVO cells with overexpressed or knocked-down CX43 was assessed through colony formation and CCK8 assays.Flow cytometry was employed to examine the effects of CX43 on the cell cycle.The in vivo effects of CX43 were validated through xenograft experiments in nude mice.Finally,the mechanisms underlying the observed effects were verified using qPCR and Western blotting techniques.Results Low expression of CX43 in colorectal cancer was identified in the TCGA database and tissue samples,and the low expression of GJA1 was associated with poor prognosis in colorectal cancer.Transcriptomic analysis of HCT116 cells overexpressing GJA1 revealed its ability to inhibit colorectal cancer proliferation by suppressing the cell cycle.Overexpression and knockdown of CX43 can inhibit or promote the proliferation of colorectal cancer through the regulation of CCND1 levels.Conclusion GJA1 is downregulated in colorectal cancer and can inhibit the proliferation of colorectal cancer by suppressing the cell cycle.