Priya, Swati and Kaur, Ekjot and Kulshrestha, Swati and Pandit, Awadhesh and Gross, Isabelle and Kumar, Nitin and Agarwal, Himanshi and Khan, Aamir and Shyam, Radhey and Bhagat, Prakash and Prabhu, Jyothi S. and Nagarajan, Perumal and Deo, S. V. S. and Bajaj, Avinash and Freund, Jean-Noël and Mukhopadhyay, Arnab and Sengupta, Sagar (2021) CDX2 inducible microRNAs sustain colon cancer by targeting multiple DNA damage response pathway factors. Journal of Cell Science. ISSN 0021-9533

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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 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.

Item Type:	Article
Subjects:	Biomedical Science Bioengineering & Devices
Depositing User:	RCB Library
Date Deposited:	29 Jul 2021 07:46
Last Modified:	29 Jul 2021 07:46
URI:	http://rcb.sciencecentral.in/id/eprint/620

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