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Regulation of ITGA 3 by the anti‐tumor miR‐199 family inhibits cancer cell migration and invasion in head and neck cancer

2017; Wiley; Volume: 108; Issue: 8 Linguagem: Inglês

10.1111/cas.13298

1349-7006

Keiichi Koshizuka, Toyoyuki Hanazawa, Naoko Kikkawa, Takayuki Arai, Atsushi Okato, Akira Kurozumi, Mayuko Kato, Koji Katada, Yoshitaka Okamoto, Naohiko Seki,

MicroRNA in disease regulation

For patients with head and neck squamous cell carcinoma ( HNSCC ), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our micro RNA (mi RNA ) expression signature by RNA sequencing showed that the miR‐199 family ( miR‐199a‐5p , miR‐199a‐3p , miR‐199b‐5 p and miR‐199b‐3p ) was significantly reduced in cancer tissues. Ectopic expression of mature mi RNA demonstrated that all members of the miR‐199 family inhibited cancer cell migration and invasion by HNSCC cell lines ( SAS and HSC 3). These findings suggested that both passenger strands and guide strands of mi RNA are involved in cancer pathogenesis. In silico database and genome‐wide gene expression analyses revealed that the gene coding for integrin α3 ( ITGA 3 ) was regulated by all members of the miR‐199 family in HNSCC cells. Knockdown of ITGA 3 significantly inhibited cancer cell migration and invasion by HNSCC cells. Moreover, overexpression of ITGA 3 was confirmed in HNSCC specimens, and high expression of ITGA 3 predicted poorer survival of the patients ( P = 0.0048). Our data revealed that both strands of pre‐ miR‐199a ( miR‐199a‐5p and miR‐199a‐3p ) and pre‐ miR‐199b ( miR‐199b‐5p and miR‐199b‐3p ) acted as anti‐tumor mi RNA in HNSCC cells. Importantly, the involvement of passenger strand mi RNA in the regulation of cellular processes is a novel concept in RNA research. Novel mi RNA ‐based approaches for HNSCC can be used to identify potential targets for the development of new therapeutic strategies.