The Role Of TEAD4 And Long Non-coding RNA AF In Colorectal Cancer

PARTⅠ THE ROLE OF LONG NON-CODING RNA AF IN COLORECTAL CANCERLong non-coding RNA(Lnc RNA)plays a very important role in colorectal carcinogenesis.OBJECTIVES: To find the Lnc RNA associated with colorectal cancer by using the method of “small samples for high throughput screening” and “large samples for validation”.To investigate the correlation between target Lnc RNA and the clinicopathologic features and the survival of colorectal cancer patients.To study the effect of target Lnc RNA on colorectal cancer cells.To explore the molecular mechanism of target Lnc RNA in colorectal cancer.METHODS: Fresh samples of matched tumors and adjacent normal tissues were used for Lnc RNA microarray analysis.The screening results were validated by quantitative real time PCR(q PCR).Combined with the corresponding clinicopathological datas and postoperative follow-up results of the colorectal cancer patients,the correlation between target Lnc RNA and pathological grading and clinical prognosis in colorectal cancer patients was retrospectively analyzed.After knockdown and overexpression of the target Lnc RNA,the changes of cell biological functions were detected by assays of cell proliferation,invasion in vitro and tumorigenicity assay in nude mice in vivo.The downstream protein of target Lnc RNA and the mechanism were explored by q PCR,Western Bolt,RNA Pull Down,CO-IP and so on.RESULT: The expression level of Lnc RNA AF was significantly higher in the tumor tissues than the adjacent normal tissues in colorectal cancer and was closely associated with tumor size,depth of cancer invasion.The high expression level of AF was associated with poor prognosis,which made it be the independent prognostic factor in multivariate analysis.Furthermore,AF could promote colorectal cancer cell proliferation both in vitro and in vivo.AF could regulate MYC by binding HSP90,which could inhibit the degradation by ubiquitination.CONCLUSION: AF can be a noval biomarker for predicting colorectal cancer and a marker of prognosis.Our study shows the importence of AF,which may be a potential therapeutic target in colorectal cancer.PARTⅡ THE ROLE OF TEAD4 IN COLORECTAL CANCERTEA domain transcription factor 4(TEAD4)plays a very important role in various cancers.OBJECTIVES: To investigate the correlation between TEAD4 and the clinicopathologic features and survival of colorectal cancer patients.To study the effect of TEAD4 on colorectal cancer cells.To explore the molecular mechanism of TEAD4 in colorectal cancer.METHODS: Matched tumor and adjacent normal tissues were used for detecting the expression of TEAD4 by q PCR.Combined with the corresponding clinicopathological datas and postoperative follow-up results of the colorectal cancer patients,the correlation between TEAD4 and pathological grading and clinical prognosis was retrospectively analyzed.After knockdown of TEAD4,the changes of cell biological functions were detected by assays of cell proliferation,invasion in vitro.The downstream protein of TEAD4 and the mechanism were explored by Western Bolt,CHIP and so on.RESULT: The expression level of TEAD4 was significantly higher in the tumor tissues than the adjacent normal tissues and was closely associated with tumor size,invasion depth and the prognosis of the colorectal cancer patients.Furthermore,TEAD4 could promote cell proliferation and invasion in colorectal cancer cells.TEAD4 could activate Hippo pathway and transcriptionly activate YAP1.CONCLUSION: TEAD4 can be a biomarker for predicting colorectal cancer and a mark of prognosis.Our study shows the importence of TEAD4,which may be a potential therapeutic target in colorectal cancer.