GSE169451
The CTCF/LncRNA-PACERR/EP300 complex in TAMs promotes the malignant progression of pancreatic ductal adenocarcinoma (PDAC) by docking at the PTGS2 promoter region
The unregulated expression of COX-2 in tams is causally related to the occurrence, development and outcome of pancreatic ductal adenocarcinoma. We describe a new basic level of transcriptional control of COX-2 expression. Constructing in vivo and in vitro TAM model lines, we found that CTCF plays a significant role in the chromatin remodeling of pancreatic cancer-related macrophages, and showed that CTCF, which acts as both a transcription factor and an insulator, establishes an open chromatin domain, and Induced the expression of LncRNA PACERR in the upstream promoter region of PTGS2. The newly transcribed LncRNA PACERR binds to the RNA binding region of CTCF to play a cis-regulatory role. The formation of CTCF/LncRNA PACERR complex contributes to the recruitment of EP300 histone acetylation transfer, which increases the global scope of histone acetylation and induces the expression of PTGS2. Our findings reveal that CTCF and LncRNA that was regulated by CTCF at the same position work together to form a complex of CTCF/LncRNA PACERR/EP300 and dock in the PTGS2 promoter region to mediate the unexpected mechanism of PTGS2 expression. And LncRNA PACERR as a new potential target for regulating the malignant progression of pancreatic cancer. Overall design: Examination of different histone modifications, chromatin accessibility and gene expression in in vivo and in vitro TAM  model lines.