DDX5 targets tissue specific RNAs to promote intestine tumorigenesis

Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that an RNA binding protein DDX5 augments C3 and FABP1 expressions post-transcriptionally to promote tumorigenesis in the colon and small intestine, respectively. Mice with epithelial-specific knockout of DDX5 are protected from intestine tumorigenesis. The identification of DDX5 as the common upstream regulator of tissue-specific oncogenic molecules provides a new therapeutic target for intestine cancers. Overall design: Primary small intestine epithelial cells and Th17 cells were harvested, crosslinked with UV, lysed and immunoprecipitated to enrich for RNA fragments bound to DDX5-containing protein complexes. Primary small intestine of 8wk adult female mice and colon epithelial cells from 120 days old Apcfl/+ CDX2Cre mice were harvested, crosslinked with UV, lysed and immunoprecipitated to enrich for RNA fragments bound to DDX5-containing protein complexes.