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CDX2 inducible microRNAs sustain colon cancer by targeting multiple DNA damage response pathway factors.
- Source :
-
Journal of Cell Science . Aug2021, Vol. 134 Issue 15, p1-19. 19p. - Publication Year :
- 2021
-
Abstract
- Meta-analysis of transcripts in colon adenocarcinoma patient tissues led to the identification of a DNA damage responsive miR signature called DNA damage sensitive miRs (DDSMs). DDSMs were experimentally validated in the cancerous colon tissues obtained from an independent cohort of colon cancer patients and in multiple cellular systems with high levels of endogenous DNA damage. All the tested DDSMs were transcriptionally upregulated by a common intestine-specific transcription factor, CDX2. Reciprocally, DDSMs were repressed via the recruitment of HDAC1/2-containing complexes onto the CDX2 promoter. These miRs downregulated multiple key targets in the DNA damage response (DDR) pathway, namely BRCA1, ATM, Chk1 (also known as CHEK1) and RNF8. CDX2 directly regulated the DDSMs, which led to increased tumor volume and metastasis in multiple preclinical models. In colon cancer patient tissues, the DDSMs negatively correlated with BRCA1 levels, were associated with decreased probability of survival and thereby could be used as a prognostic biomarker. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DNA damage
*COLON cancer
*BIOMARKERS
*MICRORNA
*BRCA genes
*CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 134
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 152123211
- Full Text :
- https://doi.org/10.1242/jcs.258601