Format

Send to

Choose Destination
Oncotarget. 2015 Sep 8;6(26):22439-51.

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

Author information

1
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
2
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
3
Department of Chemistry, York University, Toronto, Canada.
4
CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Department of Oncology, University of Oxford, Oxford, UK.
5
Ontario Institute for Cancer Research, University of Toronto, Toronto, Canada.
6
Department of Radiation Oncology, University of Toronto, Toronto, Canada.

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.

KEYWORDS:

HPGD; PGE2; miR-620; radiation resistance

PMID:
26068950
PMCID:
PMC4673174
DOI:
10.18632/oncotarget.4210
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center