Identification of Tumor Suppressive Genes Regulated by and in Head and Neck Squamous Cell Carcinoma.

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the duplex ( and ). The aims of this study were to identify networks of tumor suppressor genes regulated by and in HNSCC cells. Our functional assays showed that inhibition of and attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by in HNSCC cells. Among these targets, the low expression of seven genes ( targets: and ; targets: , and ) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (: = 0.0189; : = 0.0425; : = 0.0014; : = 0.0304; and : = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.