Inhibitory Effect Of ATOH1 On Invasion And Migration Of Colorectal Cancer And Its Mechanism

Objective: ATOH1 plays an important role in colorectal cancer.The purpose of this study was to verify the relationship between ATOH1 and EMT in colorectal cancer,and to clarify its potential mechanism.Methods: A total of 87 patients with colon cancer who received hernia treatment in the Gastrointestinal Surgery Department of the First Affiliated Hospital of China Medical University from January 2019 to June 2022 were selected as the research objects.q RTPCR was performed on 87 pairs of colorectal cancer specimens and adjacent tissues to verify the expression of ATOH1 in colorectal cancer from the RNA level.Then,31 pairs of colorectal cancer tissues and adjacent tissues were detected by Western blot,and 87 colorectal cancer specimens were detected by immunohistochemistry to verify the expression of ATOH1 in colorectal cancer from the protein level.Next,we overexpressed or knocked out ATOH1 to observe its effect on the invasion and migration ability of colorectal cancer cells and the changes of downstream proteins.Then,we stimulated colorectal cancer cells with TGFB1 to detect the expression of ATOH1 and explore whether the effect of ATOH1 on EMT is TGFβ-dependent.Finally,the effect of ATOH1 on tumor liver metastasis in nude mice was observed.Results: mRNA level of ATOH1 in colorectal cancer tissues was significantly lower than that in normal colorectal tissues(p<0.001).At the protein level,ATOH1 expression in colorectal cancer tissues was significantly lower than that in colorectal cancer tissues(p=0.0398),and low ATOH1 expression had a poor prognosis.In addition,the results showed that ATOH1 inhibited the invasion and migration ability of colorectal cancer cells.Meanwhile,ATOH1 negatively regulated the expression of Snail2 and ZEB1 proteins.The results of overexpression experiment showed that overexpression of ATOH1 inhibited the expression of ZEB1/Snail2.ATOH1 expression is down-regulated after TGFB stimulation,suggesting that the effect of ATOH1 on EMT is TGFβ-dependent.After injection of ATOH1 knockout tumor cells into mice,liver metastases increased significantly.The liver metastases in mice overexpressed with ATOH1 were significantly reduced.Conclusion: ATOH1 is significantly down-regulated in colorectal cancer tissues and inhibits the invasion and migration ability of colorectal cancer cells.It is also associated with a poor prognosis for colorectal cancer.In addition,ATOH1 affects the epithelial-tomesenchymal transition(EMT)in colorectal cancer by modulating the TGFB-dependent ZEB1/Snail2 pathway.