Role of DDX3 in the pathogenesis of inflammatory bowel disease

Saritha Tantravedi, Farhad Vesuna, Paul T. Winnard, Marise R.Heerma van Voss, Paul J. van Diest, Venu Raman

Research output: Contribution to journalArticle

Abstract

When crypt stem cells of the gastrointestinal tract become injured, the result is increased synthesis of pro-inflammatory cytokines and matrix metalloproteinases by their progeny - the colonic epithelium. Chronic inflammation of the gastrointestinal tract is a characteristic of inflammatory bowel disease, which includes Crohn's Disease and Ulcerative Colitis. In our ongoing investigation to decipher the characteristic functions of a RNA helicase gene, DDX3, we identified high DDX3 expression by immunohistochemistry of colon biopsy samples, which included chronic/mild Morbus Crohn, active Morbus Crohn, Chronic/mild Colitis Ulcerosa and active Colitis Ulcerosa in epithelium and stromal compartments. We used a small molecule inhibitor of DDX3, RK-33, on two human colonic epithelial cell lines, HCEC1CT and HCEC2CT and found that RK-33 was able to decrease expression of MMP-1, MMP-2, MMP-3, and MMP-10. Moreover, forced differentiation of a human colonic cancer cell line, HT29, resulted in decreased DDX3 levels, indicating that DDX3 contributes to the modulation of colonic epithelium differentiation. In conclusion, our results revealed novel functions of DDX3 in inflammatory bowel disease and indicate a potential for using RK-33 as a systemic therapy to promote not only differentiation of transformed colonic epithelium but also to reduce MMP expression and thus elicit a decreased inflammatory response.

Original languageEnglish (US)
Pages (from-to)115280-115289
Number of pages10
JournalOncotarget
Volume8
Issue number70
DOIs
StatePublished - Jan 1 2017

    Fingerprint

Keywords

  • Colorectal cancer
  • DDX3
  • Inflammatory bowel disease
  • MMP
  • Small molecule inhibitor

ASJC Scopus subject areas

  • Oncology

Cite this