A Research Of ACSS2 In Colorectal Cancer And Transcription Factor TEAD4 In Ulcerative Colitis

Part 1 Expression of ACSS2 in colorectal cancer and its significanceObjective To investigate the expression of acyl-CoA synthetase short-chain family member 2(ACSS2)in patients with colorectal cancer(CRC)and its biological role.Method A total of 74 CRC tissue samples and 40 normal colorectal tissues were tested by immunohistochemical staining to detect the expression of ACSS2 and analysis according to the overall survival of patients.Small interfering RNA(siRNA)was used to knock down the expression of ACSS2 in colorectal cell line and function change after knocking down was observed.Result The expression of ACSS2 was significant higher in CRC tissue than that in normal colorectal tissue(P<0.001).The positive rate of ACSS2 in nucleus was 62.2% vs.20% in CRC tissue and normal colorectal tissue(P<0.001).The using of ACSS2 siRNA successfully knocked down the expression of ACSS2 in colorectal cell line LoVo and HCT116.A mild suppression of cell proliferation and remarkable ability decline of cell migration were observed while the epithelial-mesenchymal transition marker was changed.Conclusion CRC tissues have high expression of ACSS2 and it has correlation with cell migration ability.Part 2 The role of transcription factor TEAD4 in ulcerative colitisObjective To investigate the role of transcription factor TEAD4 in ulcerative colitis and DSS induced ulcerative colitis mouse models.Method We test the expression of TEAD4 in ulcerative colitis patients by immunohistochemical.LoxP-Cre system was used to build intestinal epithelial conditional Tead4 knock out mice.5 days DSS inducing was performed to result acute colitis in mice.The inflammation severty change by Tead4 knockout was evaluated.Result The expression of TEAD4 is higher in ulcerative colitis patients than that in health control.Intestinal epithelial conditional knockout of Tead4 mice(Tead4^?IS mice)doesn't development any difference with normal condition in colon.After 5 days DSS inducing,Tead4^?IS mice exacerbate severity of colon inflammation.The proliferation and regeneration was suppressed in Tead4^?IS mice,while the amount of goblet cells reduced significantly,Conclusion Intestinal epithelial cells in ulcerative colitis patients have a higher expression of TEAD4 than that in health control.Tead4 has important role in ulcer colitis mouse model influencing intestinal epithelial cells proliferation,goblet cells differeation and local inflammation.