Oncotarget

Research Papers:

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

Xiaoyong Huang _, Samira Taeb, Sahar Jahangiri, Elina Korpela, Ivan Cadonic, Nancy Yu, Sergey Krylov, Emmanouil Fokas, Paul C. Boutros, Stanley K. Liu

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Oncotarget. 2015; 6:22439-22451. https://doi.org/10.18632/oncotarget.4210

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Abstract

Xiaoyong Huang1, Samira Taeb1, Sahar Jahangiri1, Elina Korpela1,2, Ivan Cadonic1, Nancy Yu2, Sergey N. Krylov3, Emmanouil Fokas4, Paul C. Boutros2,5, Stanley K. Liu1,2,6

1Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada

2Department of Medical Biophysics, University of Toronto, Toronto, Canada

3Department of Chemistry, York University, Toronto, Canada

4CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Department of Oncology, University of Oxford, Oxford, UK

5Ontario Institute for Cancer Research, University of Toronto, Toronto, Canada

6Department of Radiation Oncology, University of Toronto, Toronto, Canada

Correspondence to:

Stanley K. Liu, e-mail: stanley.liu@sunnybrook.ca

Keywords: miR-620, radiation resistance, HPGD, PGE2

Received: April 16, 2015     Accepted: May 22, 2015     Published: June 04, 2015

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.

Author Information

Xiaoyong Huang
Primary Contact  _

Samira Taeb

Sahar Jahangiri

Elina Korpela

Ivan Cadonic

Nancy Yu

Sergey Krylov

Emmanouil Fokas

Paul C. Boutros

Stanley K. Liu


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