In:
Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 15, No. 12 ( 2021-12-18), p. 2088-2102
Abstract:
SATB2 is a diagnostic biomarker and a favourable prognostic marker for colorectal cancer [CRC], but its role in colitis and colitis-associated colorectal cancer [CAC] is unknown. Methods Colitis was induced in intestinal epithelial-specific Satb2 knockout [Satb2 IEC-KO] and control mice using dextran sulphate sodium [DSS] . RNA-seq analysis was performed on colonic tissues, and 16S rDNA-Seq on faecal bacterial DNA from Satb2 IEC-KO and control mice. Immunohistochemistry and flow cytometry were performed to reveal the proportions of different immune cells. Chromatin immunoprecipitation [ChIP] and luciferase reporter were applied to show the regulatory role of SATB2 on SLC26A3, of which the Cl-/HCO3- exchange activity was measured fluorometrically by the pHi-sensitive dye. Bacteroides were detected by fluorescence in situ hybridisation [FISH] on colonic tissue. Results Satb2 IEC-KO mice suffered from intestinal epithelial damage spontaneously, and developed more severe colitis and CAC. The expression of SLC26A3 correlated well with SATB2 revealed by RNA-seq and The Cancer Genome Atlas [TCGA] data, and was governed by SATB2 confirmed by ChIP and luciferase reporter experiments. Decreased intestinal flora diversity was seen in Satb2 IEC-KO mice. Bacteroides were more abundant and could colonise into the inner layer of colonic mucosa in Satb2 IEC-KO mice. Faecal microbiome transplantation from Satb2 IEC-KO mice aggravated colitis and M1 macrophages infiltration. Conclusions SATB2 plays a vital role in maintaining intestinal homeostasis, and its deficiency promotes the development of colitis and CAC by influencing the intestinal luminal environment and gut flora.
Type of Medium:
Online Resource
ISSN:
1873-9946
,
1876-4479
DOI:
10.1093/ecco-jcc/jjab094
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2021
detail.hit.zdb_id:
2389631-0
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