PACER and the COX-2 Mediated Inflammatory Response
COX-2 is the rate-limiting enzyme of the arachidonic acid (AA) pathway, a crucial inflammatory response pathway dysregulated in many types of cancer. Arachidonic acid is converted by the enzyme COX-2 and downstream synthase MPGES-1 into PGE2. PGE2 is a terminal product of the AA pathway. PGE2 is a highly immunogenic molecule and an inflammatory regulator. PGE2 performs a number of important homeostatic functions, but know to be dysregulated in many types of cancer including lung cancer.
The PACER & COX-2 Gene Region
The PACER gene lies in the 5' untranslated region of COX-2. The PACER gene is transcribed anti-sense relative to the COX-2 gene.
How PACER is Known to Regulate COX-2
COX-2 is transcriptionally inactive when p50 homodimers are associated with the COX-2 promoter region. Upon a pro-inflammatory stimulus, PACER transcription is activated. PACER sequesters p50 from the COX-2 promoter allowing for the formation and binding of p50/p65 heterodimers to the COX-2 promoter. p65 contains an activation domain promoting RNA polymerase II-mediated transcription of COX-2 .
PACER in Lung Adenocarcinoma Tumor Samples
Tumor tissue exhibits high levels of PACER expression compared to normal lung tissue. Additionally, there is a significant correlation between the high levels of PACER and COX-2 expression in lung adenocarcinoma tissue samples. This is expected due to a strong functional and transcriptional link between these genes.
For more information on our work with lncRNA PACER and links to supporting references, please to refer to our recent publication, PACER lncRNA regulates COX-2 expression in lung cancer cells, in journal Oncotarget