RBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways.
JCI Insight
; 8(9)2023 05 08.
Article
em En
| MEDLINE
| ID: mdl-37014710
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Colite
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Neoplasias do Colo
Limite:
Adult
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Aged
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Animals
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Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2023
Tipo de documento:
Article