Impact of Oncogenic Targets by Tumor-Suppressive and Regulation in Head and Neck Squamous Cell Carcinoma.

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including (the guide strand) and (the passenger strand) of , were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre- ( and ) in HNSCC cells. Of these, the (guanine nucleotide-binding protein subunit alpha-12) and (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses ( = 0.0018 and = 0.0104, respectively). Direct regulation of and by in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of and was detected in clinical specimens of HNSCC through immunostaining. The involvement of (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.