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Tumor Metabolism and the Microenvironment | EK14


DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and tumorigenesis


Jan 25, 2021 12:00am ‐ Jan 25, 2021 12:00am

Description

DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and 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 the RNA binding protein DDX5 binds to the mRNA transcripts of C3 and FABP1 to augment their expressions post-transcriptionally. Knocking out DDX5 in epithelial cells protected mice from intestinal tumorigenesis and dextran sodium sulfate induced colitis. Identification of DDX5 as a common upstream regulator of tissue-specific oncogenic molecules provides an excellent therapeutic target for intestinal diseases. Tianyun Long1,5, Nazia Abbasi1,5, Yuxin Li1, , Brian A. Yee1, Benjamin S. Cho1, Juan E. Hernandez1, Evelyn Ma1, Parth R. Patel1, Debashis Sahoo4, Ibrahim M Sayed2, Nissi Varki2, Soumita Das2, Pradipta Ghosh1, 3, Gene W. Yeo1, Wendy Jia Men Huang1,6 1 Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 2 Department of Pathology, University of California San Diego, La Jolla, CA 3 Department of Medicine, University of California San Diego, La Jolla, CA 4 Department of Pediatrics, University of California San Diego, La Jolla, CA 5 These authors contributed equally

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