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

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.