Research Papers:

PACER lncRNA regulates COX-2 expression in lung cancer cells

Samuel Z. Desind, Joseph R. Iacona, Christina Y. Yu, Antonina Mitrofanova and Carol S. Lutz _

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Oncotarget. 2022; 13:291-306. https://doi.org/10.18632/oncotarget.28190

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Samuel Z. Desind1,*, Joseph R. Iacona1,*, Christina Y. Yu2, Antonina Mitrofanova2,3 and Carol S. Lutz1

1 Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers Biomedical and Health Sciences, New Jersey Medical School, School of Graduate Studies, Newark, NJ 07103, USA

2 Department of Health Informatics, Rutgers School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ 07107, USA

3 Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA

* These authors contributed equally to this work

Correspondence to:

Carol S. Lutz, email: [email protected]

Keywords: PACER; COX-2; PGE2; lung adenocarcinoma; inflammation

Received: November 24, 2021     Accepted: January 25, 2022     Published: February 04, 2022

Copyright: © 2022 Desind et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 (PGE2) induces both PACER and COX-2 expression, suggesting a PGE2-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.

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