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PACER lncRNA Regulates COX‐2 Expression in Lung Cancer Cell Lines
Author(s) -
Desind Samuel Z.,
Iacona Joseph R.,
Yu Christina Y.,
Mitrofanova Antonina,
Lutz Carol S.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.l8032
Subject(s) - gene knockdown , biology , cancer research , transcription factor , lung cancer , inflammation , medicine , gene , immunology , genetics
Long noncoding RNAs (lncRNAs) are known to regulate gene expression; however, in many cases, the mechanism of this regulation is unknown. One novel lncRNA relevant to inflammation and arachidonic acid (AA) metabolism is the p50‐associated COX‐2 extragenic RNA (PACER). We focused our research on the regulation of PACER in lung cancer. While the function of PACER is not entirely understood, PACER is known to play a role in inflammation‐associated conditions. Our data suggest that PACER is critically involved in COX‐2 transcription and dysregulation in lung cancer cells. Our analysis of The Cancer Genome Atlas (TCGA) expression data revealed that PACER expression is significantly higher in lung adenocarcinomas than normal lung tissues. Additionally, we discovered that elevated PACER expression strongly correlates with COX‐2 expression in lung adenocarcinoma patients. Specific siRNA‐mediated knockdown of PACER decreases COX‐2 expression indicating a direct relationship. Additionally, we show that PACER expression is induced upon treatment with proinflammatory cytokines to mimic inflammation. Treatment with prostaglandin E2 (PGE 2 ) induces both PACER and COX‐2 expression, suggesting a PGE 2 ‐mediated feedback loop. Inhibition of COX‐2 with celecoxib decreased PACER expression, confirming this self‐regulatory process. Significant overlap between the COX‐2 promotor and the PACER promotor led us to investigate their transcriptional regulatory mechanisms. Treatment with pharmacologic inhibitors of NF‐ϰB or AP‐1 showed a modest effect on both PACER and COX‐2 expression but did not eliminate expression. These data suggest that the regulation of expression of both PACER and COX‐2 is complex and intricately linked.