Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UMLS:C0001339 (
acute pancreatitis
)
10,593
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
CASC2
(Cancer Susceptibility Candidate 2) was significantly upregulated in the pancreatic tissues from AP patients. Knockdown or overexpression of
CASC2
in vitro
could specifically repress or induce the expression of two proinflammatory cytokines including
IL6
(Interleukin 6) and
IL17
, respectively. Changing the expression levels of several transcription factors that were predicted to bind to the promoter of
CASC2
, we found c-MYC could specifically regulate the expression of
CASC2
. 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
CASC2
and thus led to the upregulation of
IL6
and
IL17
. Moreover, we identified that decreased DNA methylation levels in the promoters of
CtBPs
and inflammatory stimuli coactivated the expression of
CtBPs.
Collectively, we identified a new signaling pathway in which DNA methylation and inflammatory stimuli coregulate the CPM complex to activate
CASC2
expression, whose induction further activates the expression of
IL6
and
IL17
, eventually aggravating inflammation response and causing the pathology of AP.
...
PMID: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. 3254 59
