Oncotarget

Research Papers:

Inhibition of integrin β1-mediated oncogenic signalling by the antitumor microRNA-29 family in head and neck squamous cell carcinoma

Keiichi Koshizuka, Naoko Kikkawa, Toyoyuki Hanazawa, Yasutaka Yamada, Atsushi Okato, Takayuki Arai, Koji Katada, Yoshitaka Okamoto and Naohiko Seki _

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Oncotarget. 2018; 9:3663-3676. https://doi.org/10.18632/oncotarget.23194

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Abstract

Keiichi Koshizuka1,2, Naoko Kikkawa2, Toyoyuki Hanazawa2, Yasutaka Yamada1, Atsushi Okato1, Takayuki Arai1, Koji Katada2, Yoshitaka Okamoto2 and Naohiko Seki1

1Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan

2Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

Correspondence to:

Naohiko Seki, email: [email protected]

Keywords: microRNA; miR-29a; miR-29b; miR-29c; ITGB1

Received: October 17, 2017     Accepted: December 01, 2017     Published: December 11, 2017

ABSTRACT

Due to their aggressive behavior, local recurrence and distant metastasis, survival rate of advanced stage of the patients with head and neck squamous cell carcinoma (HNSCC) is very poor. Currently available epidermal growth factor receptor (EGFR)-targeted therapies are not considered curative for HNSCC. Therefore, novel approaches for identification of therapeutic targets in HNSCC are needed. All members of the miRNA-29 family (miR-29a, miR-29b, and miR-29c) were downregulated in HNSCC tissues by analysis of RNA-sequencing based microRNA (miRNA) expression signature. Ectopic expression of mature miRNAs demonstrated that the miR-29 family inhibited cancer cell migration and invasion by HNSCC cell lines. Comprehensive gene expression studies and in silico database analyses were revealed that integrin β1 (ITGB1) was regulated by the miR-29family in HNSCC cells. Overexpression of ITGB1 was confirmed in HNSCC specimens, and high expression of ITGB1 significantly predicted poor survival in patients with HNSCC (p = 0.00463). Knockdown of ITGB1 significantly inhibited cancer cell migration and invasion through regulating downstream of ITGB1-mediated oncogenic signalling. In conclusion, regulation of the antitumor miR-29 family affected integrin-mediated oncogenic signalling to modulate HNSCC pathogenesis; these molecules may be novel therapeutic targets for HNSCC.


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