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RBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory

Saeed Soleymanjahi1, Valerie Blanc1, Elizabeth A Molitor1

  • 1Division of Gastroenterology, Department of Medicine.

JCI Insight
|April 4, 2023
PubMed

Insights

RNA-binding protein 47 (RBM47) regulates intestinal growth and inflammation. Loss of RBM47 in mice altered proliferation and protected against colitis but promoted polyposis, indicating a complex role in intestinal tumorigenesis.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Oncology

Background:

  • The role of RNA-binding protein 47 (RBM47) in adult intestinal development and disease remains largely unknown.
  • RBM47 is essential for embryonic endoderm development.

Purpose of the Study:

  • To investigate the function of RBM47 in the adult intestine, focusing on its role in proliferation, response to injury, and tumorigenesis.
  • To examine RBM47's involvement in human colorectal polyps and colon carcinoma.

Main Methods:

  • Generation and analysis of intestine-specific Rbm47-knockout (Rbm47-IKO) mice.
  • Induction of intestinal injury (radiation and chemical-induced colitis) in Rbm47-IKO mice.
  • Crossbreeding Rbm47-IKO mice with ApcMin/+ mice to study polyposis.
  • Analysis of human colorectal cancer and polyp tissues.
  • Investigation of RBM47 expression in public databases.

Main Results:

  • Rbm47-IKO mice exhibited increased intestinal proliferation, abnormal villus morphology, and altered cellularity.
  • Rbm47-IKO mice showed enhanced adaptation to radiation injury and protection against chemical-induced colitis.
  • Upregulation of antioxidant, Wnt signaling, stem cell, and developmental genes was observed in Rbm47-IKO intestines.
  • Rbm47-IKO mice were protected against colitis-associated cancer but developed spontaneous polyposis with age.
  • Rbm47-IKO ApcMin/+ mice displayed an increased intestinal polyp burden.
  • Decreased RBM47 mRNA levels and altered tight junction protein 1 mRNA splicing were found in human colorectal cancer tissues.
  • Stage-specific reduction of RBM47 expression in colorectal cancer correlated with decreased overall survival.

Conclusions:

  • RBM47 acts as a cell-intrinsic regulator of intestinal growth, inflammation, and tumorigenic pathways.
  • RBM47 plays a dual role in intestinal tumorigenesis, offering protection against certain cancers while potentially promoting polyposis.
  • Downregulation of RBM47 is associated with colorectal cancer progression and poorer survival in humans.
Keywords:
Colorectal cancerGastroenterologyInflammationRNA processing

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