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Animal studies indicated that P1 promoter-driven hepatocyte nuclear factor 4 alpha (HFN4A)prevents carcinogenesis in colitis.But the function of total HNF4A protein has not been fully inves-tigated,and it was assumed to be involved in the colitis-neoplastic sequence.The aim of this study was to determine the clinical value of total P1-/P2-driven HNF4A combined with β-catenin in the colitis-neoplastic sequence.A total of 69 samples,including 4 normal colon tissues,16 sporadic colorectal cancer (CRC) tissues,35 inflammatory bowel disease (IBD) tissues,and 14IBD-associated low-grade dysplasia tissues,were collected to assess P1-/P2-driven HNF4A and β-catenin expres-sions by immunohistochemical assay.In addition,a colonic epithelial cell line Caco2 with stable P1-/P2-driven HNF4A knockdown was constructed.β-Catenin expression and skeleton structure were determined in the transfected cells by western blot analysis and immunofluorescence assay respectively.Increased expression of nuclear P1-/P2-driven HNF4A was observed in the colitis-associated colorectal neoplasm and sporadic CRC samples,compared with that in colitis samples.The parallel alterations between cytoplasmic β-catenin and nuclear P1-/P2-driven HNF4A were also verified.Silencing of P1-/P2-driven HNF4A expression in Caco2 cells decreased β-catenin expres-sion and F-actin formation.Our results confirmed the elevated expressions of nuclear P1-/P2-driven HNF4A and cytoplasmic β-catenin in the colitis-neoplastic sequence,and both of them may be used as potential biomarkers to predict low-grade dysplasia.