MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing
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Szu-Yuan Wu1,2,3,4, Alexander T.H. Wu5, Shing-Hwa Liu1,6,7
1Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
2Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
3Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
4Department of Biotechnology, Hungkuang University, Taichung, Taiwan
5The Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan
6Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan
7Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
Shing-Hwa Liu, email: [email protected]
Keywords: miR-17-5p, OC3 cells, p53, radiation, apoptosis
Received: February 27, 2016 Accepted: May 26, 2016 Published: June 06, 2016
Betel nut chewing is associated with oral cavity cancer. Radiotherapy is one of the therapeutic approaches. Here, we used miR-17-5p antisense oligonucleotides (AS-ODNs) and human apoptosis protein array to clarify which apoptosis-related proteins are increased or decreased by miR-17-5p in betel nut chewing- oral squamous cell carcinoma OC3 cells. Furthermore, miR-17-5p AS-ODN was used to evaluate the radio-sensitization effects both in vitro and in vivo. An OC3 xenograft tumor model in severe combined immunodeficiency mice was used to determine the effect of miR-17-5p AS ODN on tumor irradiation. We simultaneously detected the relative expressions of 35 apoptosis-related proteins in irradiated OC3 cells that were treated with miR-17-5p AS-ODN or a control ODN. Several proteins, including p21, p53, TNF RI, FADD, cIAP-1, HIF-1α, and TRAIL R1, were found to be up- or downregulated by miR-17-5p in OC3 cells; their expression patterns were also confirmed by Western blotting. We further clarified the role of p53 in irradiated OC3 cells, using a p53 overexpression strategy. The results revealed that the enhancement of p53 expression significantly enhanced radiation-induced G2/M arrest of the OC3 cells. In the in vivo study, treatment of miR-17-5p AS-ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results suggest that miR-17-5p increases or decreases apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells.
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