biostudies-literatureSoleymanjahi SLawrence Pakula MD IBD Innovation fundNCI-NIHNIDDK NIH HHSNIAID NIH HHSU.S. Department of DefenseNCI NIH HHSNational Institutes of HealthNIAIDNIDDKAmerican Gastroenterological AssociationCrohn’s and Colitis Foundation of Americae161118https://www.ebi.ac.uk/biostudies/studies/S-EPMC10243830biostudies-literatureUnknown8(9)RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and developmental genes. Furthermore, Rbm47-IKO mice were protected against colitis-associated cancer. By contrast, aged Rbm47-IKO mice developed spontaneous polyposis, and Rbm47-IKO ApcMin/+ mice manifested an increased intestinal polyp burden. RBM47 mRNA was decreased in human colorectal cancer versus paired normal tissue, along with alternative splicing of tight junction protein 1 mRNA. Public databases revealed stage-specific reduction in RBM47 expression in colorectal cancer associated independently with decreased overall survival. These findings implicate RBM47 as a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways.JCI insightRBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways.PMC10243830R01 CA246208CA239645DK109384P30DK056338K08 DK132496DK125296,DK124274P30 DK052574R01 CA239645Award No. W81XWH-20-1-630CCF#648423NIAID R21 AI156236Detailed belowR01 DK105129no number assignedBiobankP30-DK-52574,AITAC,PAMOCP30 DK056338CA230289R21 AI156236DK-119437,DK-128169AGA2021-5101DK128169DK106382,Xie YSoleymanjahi SGazit VByrnes KBrown JWBlanc VAlvarado DMRubin DCDavidson NOMolitor EAMills JCLiu TCCiorba MAfalseRBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways.RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and developmental genes. Furthermore, Rbm47-IKO mice were protected against colitis-associated cancer. By contrast, aged Rbm47-IKO mice developed spontaneous polyposis, and Rbm47-IKO ApcMin/+ mice manifested an increased intestinal polyp burden. RBM47 mRNA was decreased in human colorectal cancer versus paired normal tissue, along with alternative splicing of tight junction protein 1 mRNA. Public databases revealed stage-specific reduction in RBM47 expression in colorectal cancer associated independently with decreased overall survival. These findings implicate RBM47 as a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways.2023-01-01T00:00:00Z2023 May2024-11-21T05:43:07.967Z2024-11-21T05:43:07.967ZS-EPMC102438303701471010.1172/jci.insight.161118