miR-708-5p targets oncogenic prostaglandin E2 production to suppress a pro-tumorigenic phenotype in lung cancer cells

Nicholas J. Monteleone, Carol S. Lutz

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Many cancers maintain an inflammatory microenvironment to promote their growth. Lung cancer is of particular importance, as it is the deadliest cancer worldwide. One inflammatory pathway commonly dysregulated in cancer is the metabolism of arachidonic acid (AA) by Cyclooxygenase-2 (COX-2) and microsomal Prostaglandin E Synthase 1 (mPGES-1) into Prostaglandin E2 (PGE2). While researchers have identified PGE2's pro-tumorigenic functions, the mechanisms governing overexpression of COX-2 and mPGES-1 are incompletely understood. MicroRNAs (miRNAs) are important post-transcriptional regulators commonly dysregulated in cancer. Interestingly, miR-708-5p (miR-708) is predicted to target both COX-2 and mPGES-1. In this study, we show that high miR-708 expression is associated with survival rates in lung squamous cell carcinoma patients. miR-708 also represses PGE2 production by suppressing both COX-2 and mPGES-1 expression in lung cancer cells. miR-708 regulation of COX-2 and mPGES-1 is mediated through targeting of their 3′ untranslated regions (UTRs). Moreover, miR-708 decreases proliferation, survival, and migration of lung cancer cells, which can be partially attributed to miR-708's inhibition of PGE2 signaling. Lastly, we identify novel miR-708 predicted targets and possible regulators of miR-708 expression in lung cancer. Collectively, these data demonstrate that dysregulated miR-708 expression contributes to exacerbated PGE2 production, leading to an enhanced pro-tumorigenic phenotype in lung cancer cells.

Original languageEnglish (US)
Pages (from-to)2464-2483
Number of pages20
Issue number26
StatePublished - Jun 30 2020

All Science Journal Classification (ASJC) codes

  • Oncology


  • COX-2
  • Lung cancer
  • MPGES-1
  • MiR-708
  • MiR-708-5p


Dive into the research topics of 'miR-708-5p targets oncogenic prostaglandin E2 production to suppress a pro-tumorigenic phenotype in lung cancer cells'. Together they form a unique fingerprint.

Cite this