Portal de Periódicos da CAPES

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

2017; Impact Journals LLC; Volume: 9; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.23194

1949-2553

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

Circular RNAs in diseases

// Keiichi Koshizuka 1, 2 , Naoko Kikkawa 2 , Toyoyuki Hanazawa 2 , Yasutaka Yamada 1 , Atsushi Okato 1 , Takayuki Arai 1 , Koji Katada 2 , Yoshitaka Okamoto 2 and Naohiko Seki 1 1 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan 2 Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan Correspondence to: Naohiko Seki, email: naoseki@faculty.chiba-u.jp 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-29 family 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.