Inflammation and DNA methylation coregulate the CtBP-PCAF-c-MYC transcriptional complex to activate the expression of a long non-coding RNA CASC2 in acute pancreatitis

Long non-coding RNAs (lncRNAs) are emerging as important regulators involved in the pathogenesis of many diseases. However, it is still unknown if they contribute to the occurrence of acute pancreatitis (AP). Here, we identified a lncRNA (Cancer Susceptibility Candidate 2) was significantly upregula...

Full description

Saved in:
Bibliographic Details
Published in:International journal of biological sciences 2020-01, Vol.16 (12), p.2116-2130
Main Authors: Zeng, Jun, Chen, Jian-Yong, Meng, Jun, Chen, Zhi
Format: Article
Language:English
Subjects:
Biopsy
Bladder cancer
c-Myc protein
Cell growth
Colorectal cancer
Cytokines
Deoxyribonucleic acid
DNA
DNA methylation
Endoscopy
Gastric cancer
Gene expression
Immunoprecipitation
Inflammation
Interleukin 1
Interleukin 17
Interleukin 6
Kinases
Mass spectrometry
Mass spectroscopy
Myc protein
Non-coding RNA
Pancreas
Pancreatic cancer
Pancreatitis
Pathogenesis
Proteins
Research Paper
Signal transduction
Stimuli
Transcription factors
Tumor necrosis factor-TNF
Ultrasonic imaging
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Long non-coding RNAs (lncRNAs) are emerging as important regulators involved in the pathogenesis of many diseases. However, it is still unknown if they contribute to the occurrence of acute pancreatitis (AP). Here, we identified a lncRNA (Cancer Susceptibility Candidate 2) was significantly upregulated in the pancreatic tissues from AP patients. Knockdown or overexpression of could specifically repress or induce the expression of two proinflammatory cytokines including (Interleukin 6) and , respectively. Changing the expression levels of several transcription factors that were predicted to bind to the promoter of , we found c-MYC could specifically regulate the expression of . Using immunoprecipitation, mass spectrometry, and co-immunoprecipitation assays, we proved that c-MYC assembled a transcriptional complex with PCAF (p300/CBP-associated Factor) and CtBP1/2 (C-terminal Binding Protein 1 and 2), terming as the CtBP-PCAF-c-MYC (CPM) complex. Further investigation revealed that CtBPs were amplified in the pancreatic tissues from AP patients and they functioned as coactivators to induce the expression of and thus led to the upregulation of and . Moreover, we identified that decreased DNA methylation levels in the promoters of and inflammatory stimuli coactivated the expression of Collectively, we identified a new signaling pathway in which DNA methylation and inflammatory stimuli coregulate the CPM complex to activate expression, whose induction further activates the expression of and , eventually aggravating inflammation response and causing the pathology of AP.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.43557