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

Life science alliance · 2020 · Vol. 3 (10)

Abstract

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 <i>C3</i> and <i>Fabp1</i> to augment their expressions posttranscriptionally. Knocking out DDX5 in epithelial cells protected mice from intestinal tumorigenesis and dextran sodium sulfate (DSS)-induced colitis. Identification of DDX5 as a common upstream regulator of tissue-specific oncogenic molecules provides an excellent therapeutic target for intestinal diseases.

Publication Types

["Journal Article", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't"]

Keywords

[]

MeSH Terms

["Animals", "Carcinogenesis", "Colitis", "Complement C3", "DEAD-box RNA Helicases", "Dextran Sulfate", "Epithelial Cells", "Fatty Acid-Binding Proteins", "Female", "Gene Expression", "Gene Expression Regulation, Neoplastic", "Inflammation", "Intestinal Mucosa", "Intestine, Small", "Intestines", "Male", "Mice", "Mice, Inbred C57BL", "Oncogenes", "Signal Transduction"]

Funding

S10 OD026929 NIH HHS (United States)
R01 HG004659 NHGRI NIH HHS (United States)
P30 CA023100 NCI NIH HHS (United States)
T32 CA067754 NCI NIH HHS (United States)
U41 HG009889 NHGRI NIH HHS (United States)
R01 GM124494 NIGMS NIH HHS (United States)
R01 CA238042 NCI NIH HHS (United States)
R01 CA100768 NCI NIH HHS (United States)
UG3 TR003355 NCATS NIH HHS (United States)
R01 DK107585 NIDDK NIH HHS (United States)
R01 AI141630 NIAID NIH HHS (United States)
UG3 TR002968 NCATS NIH HHS (United States)
UH3 TR002968 NCATS NIH HHS (United States)
R01 GM138385 NIGMS NIH HHS (United States)
R00 CA151673 NCI NIH HHS (United States)

Linked Datasets (2)

GSE123881 GSE via ncbi_elink
GEO

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

Mus musculus
8 data files
FileTypeSize
NA01_S1_L008_R1_001.fastq.gz RNA-Seq 3.7 GB
NA02_S2_L008_R1_001.fastq.gz RNA-Seq 1.7 GB
NA03_S3_L008_R1_001.fastq.gz RNA-Seq 2.4 GB
NA04_S4_L008_R1_001.fastq.gz RNA-Seq 2.8 GB
NA05_S5_L008_R1_001.fastq.gz RNA-Seq 2.8 GB
NA06_S6_L008_R1_001.fastq.gz RNA-Seq 3.0 GB
NA07_S7_L008_R1_001.fastq.gz RNA-Seq 3.2 GB
NA08_S8_L008_R1_001.fastq.gz RNA-Seq 2.9 GB
GSE124023 GSE via ncbi_elink
GEO

DDX5 targets tissue specific RNAs to promote intestine tumorigenesis

Mus musculus
12 data files
FileTypeSize
INPUT_G1_S36_L003_R1_001.fastq RIP-Seq 1.5 GB
INPUT_G2_S38_L003_R1_001.fastq RIP-Seq 2.0 GB
IP_G1_S37_L003_R1_001.fastq RIP-Seq 1.5 GB
IP_G2_S39_L003_R1_001.fastq RIP-Seq 736.2 MB
mAb_IN_1_Ep_S35_L003_R1_001.fastq.gz RIP-Seq 550.5 MB
mAb_IN_2_Ep_S37_L003_R1_001.fastq.gz RIP-Seq 695.1 MB
mAb_IP_1_Ep_S36_L003_R1_001.fastq.gz RIP-Seq 746.7 MB
mAb_IP_2_Ep_S38_L003_R1_001.fastq.gz RIP-Seq 533.2 MB
rAb_IN_1_Ep_S39_L003_R1_001.fastq.gz RIP-Seq 631.1 MB
rAb_IN_2_Ep_S41_L003_R1_001.fastq.gz RIP-Seq 623.4 MB
rAb_IP_1_Ep_S40_L003_R1_001.fastq.gz RIP-Seq 457.5 MB
rAb_IP_2_Ep_S42_L003_R1_001.fastq.gz RIP-Seq 547.6 MB

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These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.

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Analysis Pipelines (11)

geo_data_processing GSE123881
eCLIP geo_data_processing GSE124023
geo_data_processing GSE13067
Microarray geo_data_processing GSE14333
Microarray geo_data_processing GSE17536
geo_data_processing GSE17538
Microarray geo_data_processing GSE31595
Microarray geo_data_processing GSE33113
geo_data_processing GSE37892
geo_data_processing GSE5851
Microarray geo_data_processing GSE87211