Impact of <i>miR-1</i>/<i>miR-133</i> Clustered miRNAs: <i>PFN2</i> Facilitates Malignant Phenotypes in Head and Neck Squamous Cell Carcinoma

Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of <i>miR-1-3p</i>, <i>miR-206</i>, <i>miR-133a-3p</i>, and <i>miR-133b</i> were significantly suppressed in cancer specimens. Seed sequences of <i>miR-1-3p</i>/<i>miR-206</i> and <i>miR-133a-3p</i>/<i>miR-133b</i> are identical. Interestingly, <i>miR-1-3p</i>/<i>miR-133a-3p</i> and <i>miR-206</i>/<i>miR-133b</i> are clustered in the human genome. We hypothesized that the genes coordinately controlled by these miRNAs are closely involved in the malignant transformation of HNSCC. Our in silico analysis identified a total of 28 genes that had putative <i>miR-1-3p</i>/<i>miR-133a-3p</i> and <i>miR-206</i>/<i>miR-133b</i> binding sites. Moreover, their expression levels were upregulated in HNSCC tissues. Multivariate Cox regression analyses showed that expression of <i>PFN2</i> and <i>PSEN1</i> were independent prognostic factors for patients with HNSCC (<i>p</i> < 0.05). Notably, four miRNAs (i.e., <i>miR-1-3p, miR-206, miR-133a-3p</i>, and <i>miR-133b</i>) directly bound the 3′untranslated region of <i>PFN2</i> and controlled expression of the gene in HNSCC cells. Overexpression of <i>PFN2</i> was confirmed in clinical specimens, and its aberrant expression facilitated cancer cell migration and invasion abilities. Our miRNA-based strategy continues to uncover novel genes closely involved in the oncogenesis of HNSCC.