The tumor-suppressive microRNA-23b/27b cluster regulates the MET oncogene in oral squamous cell carcinoma

Abstract

Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that two clustered miRNAs, microRNA-23b (miR-23b) and microRNA-27b (miR27b), were significantly reduced in cancer tissues. Few reports have provided functional analyses of these clustered miRNAs in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the functional significance of miR-23b and miR-27b i n O SCC a nd t o i dentify n ovel miR-23b/27b-mediated cancer pathways and target genes involved in OSCC oncogenesis and metastasis. Expression levels of miR-23b and miR-27b were significantly reduced in OSCC specimens. Restoration of miR-23b or miR-27b in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analyses and luciferase reporter assays showed that the receptor tyrosine kinase MET, was directly regulated by these miRNAs. Moreover, downregulating the MET gene by use of siRNA significantly inhibited cell migration and invasion by OSCC cells. The identification of novel molecular pathways regulated by miR-23b and miR-27b may lead to a better understanding of the oncogenesis and metastasis of this disease.