The Function And Mechanism Of Connexin 43 In The Progression Of Colorectal Cancer

Background: Colorectal cancer is one of the most common malignancies,with third highest incidence among all cancers.Gap junction is an important structure for information exchange between cells.Connexin is a major component of gap junction,and its expression and distribution changes affect the development of various diseases.Cx43 is a member of the connexin family and exhibits abnormal up-or down-regulation in a variety of malignancies including neuroblastoma,prostate cancer,breast cancer,skin cancer,and colorectal cancer.Cx43 is the most widely studied molecule in the connexin family.It has been reported in the literature that the expression of Cx43 in normal colorectal tissues is higher than that in corresponding colorectal cancer tissues.The difference in the distribution of Cx43 in cellellar compartment can predict the prognosis of colorectal cancer patients.At present,the role of Cx43 in the development of colorectal cancer remains unclear and the involved mechanism needs further study.Methods: We first used Western Blot to investigate the basal expression of Cx43 in human colorectal cancer tissues and colon cancer cell lines.Cx43 overexpressing colon cancer cell lines were constructed,and scratch test and Transwell migration and invasion experiments were performed to explore the phenotypic differences between groups.Western Blot was used to explore the relationship with EMT.The effects of chemotherapeutic drugs oxaliplatin and Cx43 on the proliferation of colon cancer cell line(HCT116)(CCK8 assay)were investigated by bioinformatic analysis(TCGA colon cancer data,GEO data GSE10405 chip)and the results of bioinformatic analysis were verified by q PCR.Immunohistochemical(IHC)staining was performed in 75 pairs of colorectal cancer tissues and paracancerous tissues in our center.We combined IHC staining scores with clinicopathological features of colorectal patients to analyze relationship between.Results: The expression level of Cx43 in human colorectal cancer tissues was lower than that in adjacent tissues.Overexpression of Cx43 in colon cancer cell lines SW480 and SW48 significantly decresaed the migration and invasion of cells,increased the expression of E-Cadherin and ZO-1,and decreased the expression of N-Cadherin,Vimentin and Snail.The bioinformatic analysis showed that Cx43 was negatively correlated with the base-excision repair pathway.Overexpression of Cx43 in the colon cancer cell line HCT116 enhanced the killing effect of oxaliplatin on cells,but the the results of q PCR in HCT116 cell line didn’t match the predicted gene.Immunohistochemistry of human colorectal cancer tissues showed that the expression of Cx43 in colorectal cancer tissues was significantly lower than that in adjacent tissues.The expression of Cx43 in patients with T3+T4 tumor T was lower than that in patients with T1+T2.Conclusions: Cx43 plays a tumor suppressor-like role in the development of colorectal cancer,which inhibits metastasis through regulating EMT process.The research provides a theoretical basis for screening of new targets for colorectal cancer drug treatment.