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dc.contributor.authorMonteleone, Nicholas J.
dc.contributor.authorMoore, Ashleigh E.
dc.contributor.authorIacona, Joseph R.
dc.contributor.authorLutz, Carol S.
dc.contributor.authorDixon, Dan A.
dc.identifier.citationMonteleone, N. J., Moore, A. E., Iacona, J. R., Lutz, C. S., & Dixon, D. A. (2019). miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer. Scientific reports, 9(1), 5405.
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractElevated prostaglandin E2 (PGE2) levels are observed in colorectal cancer (CRC) patients, and this increase is associated with poor prognosis. Increased synthesis of PGE2 in CRC has been shown to occur through COX-2-dependent mechanisms; however, loss of the PGE2-catabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, HPGD), in colonic tumors contributes to increased prostaglandin levels and poor patient survival. While loss of 15-PGDH can occur through transcriptional mechanisms, we demonstrate that 15-PGDH can be additionally regulated by a miRNA-mediated mechanism. We show that 15-PGDH and miR-21 are inversely correlated in CRC patients, with increased miR-21 levels associating with low 15-PGDH expression. 15-PGDH can be directly regulated by miR-21 through distinct sites in its 3′ untranslated region (3′UTR), and miR-21 expression in CRC cells attenuates 15-PGDH and promotes increased PGE2 levels. Additionally, epithelial growth factor (EGF) signaling suppresses 15-PGDH expression while simultaneously enhancing miR-21 levels. miR-21 inhibition represses CRC cell proliferation, which is enhanced with EGF receptor (EGFR) inhibition. These findings present a novel regulatory mechanism of 15-PGDH by miR-21, and how dysregulated expression of miR-21 may contribute to loss of 15-PGDH expression and promote CRC progression via increased accumulation of PGE2.en_US
dc.description.sponsorshipNIH R01 CA134609en_US
dc.description.sponsorshipNIH R01 AR069044en_US
dc.description.sponsorshipNIH/NCI Cancer Center Support Grant (P30 CA168524)en_US
dc.description.sponsorshipNew Jersey Commission on Cancer Researchen_US
dc.description.sponsorshipAmerican Heart Association (15GRNT23240019)en_US
dc.publisherNature Researchen_US
dc.rightsCopyright © 2019, The Author(s)en_US
dc.titlemiR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon canceren_US
kusw.kuauthorDixon, Dan A.
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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