miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD).

Abstract	MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation resistance.
Authors	Xiaoyong Huang, Samira Taeb, Sahar Jahangiri, Elina Korpela, Ivan Cadonic, Nancy Yu, Sergey N Krylov, Emmanouil Fokas, Paul C Boutros, Stanley K Liu
Journal	Oncotarget (Oncotarget) Vol. 6 Issue 26 Pg. 22439-51 (Sep 08 2015) ISSN: 1949-2553 [Electronic] United States
PMID	26068950 (Publication Type: Journal Article)
Chemical References	MIRN620 microRNA, human MicroRNAs RNA, Small Interfering Hydroxyprostaglandin Dehydrogenases 15-hydroxyprostaglandin dehydrogenase Dinoprostone
Topics	Animals Breast Neoplasms (enzymology, genetics, radiotherapy, therapy) Cell Line, Tumor Dinoprostone (metabolism, pharmacology) Female Humans Hydroxyprostaglandin Dehydrogenases (genetics, metabolism) Male Mice Mice, Nude MicroRNAs (administration & dosage, genetics) Neoplasms (enzymology, genetics, radiotherapy, therapy) Pancreatic Neoplasms (enzymology, genetics, radiotherapy, therapy) Prostatic Neoplasms (enzymology, genetics, radiotherapy, therapy) RNA, Small Interfering (administration & dosage, genetics) Radiation Tolerance (drug effects, genetics) Radiotherapy, Adjuvant Transfection Xenograft Model Antitumor Assays

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