The role of miR-21 as a predictive biomarker and a potential target to improve the effects of chemoradiotherapy against head and neck squamous cell carcinoma

Author:

Ishinaga Hajime1,Okugawa Yoshinaga23,Hou Bo4,He Feng4,Yin Chengzeng2,Murata Mariko4,Toiyama Yuji2,Takeuchi Kazuhiko1

Affiliation:

1. Department of Otorhinolaryngology – Head & Neck Surgery, Mie University Graduate School of Medicine , Edobashi, Tsu, Mie 514-8507 , Japan

2. Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine , Edobashi, Tsu, Mie 514-8507 , Japan

3. Department of Genomic Medicine, Mie University Hospital , Edobashi, Tsu, Mie 514-8507 , Japan

4. Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine , Edobashi, Tsu, Mie 514-8507 , Japan

Abstract

Abstract This study aimed to clarify whether circulating miR-21 represents a predictive biomarker in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, and to investigate the effect of miR-21 inhibitor for chemoradiation in human SCC cells. Plasma samples were obtained from 22 patients with HNSCC and 25 non-cancer volunteers. Plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. The effects of miR-21 inhibitor in human SCC cells were investigated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and western blot analysis. As a result, plasma miR-21 expression was higher in HNSCC patients than in control patients (P < 0.001). Seven patients with recurrence showed significantly higher plasma miR-21 than the 15 patients without recurrence. And high miR-21 expression group showed poor overall survival. Moreover, miR-21 inhibition significantly enhanced cisplatin- or radiation-induced apoptosis. Western blot analysis suggested the programmed cell death 4 protein as a potential target of miR-21 in relation to apoptosis. In conclusion, this study provides new insights into the role of miR-21 as a predictive biomarker for HNSCC treated with chemoradiotherapy and suggests a potential target to improve the effects of chemoradiotherapy against HNSCC.

Funder

EKIDEN

Japan Society for the Promotion of Science London

Mie University Hospital

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Radiology, Nuclear Medicine and imaging,Radiation

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