title: 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.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Samira
authors.initials: S
authors.lastname: Taeb
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Sahar
authors.initials: S
authors.lastname: Jahangiri
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Elina
authors.initials: E
authors.lastname: Korpela
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cadonic
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Chemistry, York University, Toronto, Canada.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Krylov
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Fokas
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, University of Toronto, Toronto, Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: Stanley K
authors.initials: SK
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D018714:Radiotherapy, Adjuvant; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C000594137:MIRN620 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone
keywords: HPGD; PGE2; miR-620; radiation resistance