Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling

Abstract

MicroRNAs (miRNAs) are noncoding RNAs with specific regulatory role in gene expression. Recent reports suggested their involvement in human malignancies. Currently, there is no information concerning miRNA expression and functions in squamous cell carcinoma (SCC) of tongue. In this study, we evaluated the expression patterns of 156 mature miRNAs in tongue SCC using Taqman-based microRNA assays. Of these 156 miRNAs, miR-133a and miR-133b were significantly reduced in tongue SCC cells in comparison with the paired normal epithelial cells. Tongue SCC cell lines transfected with miR-133a and miR-133b precursors displayed reduction in proliferation rate. In addition, the number of apoptotic cells was increased in response to the introduction of precursors. Computational target gene prediction suggested that both miR-133a and miR-133b are targeting transcript of pyruvate kinase type M2 (PKM2), a potential oncogene in solid cancers. In tongue SCC cell lines, PKM2 expression was reduced in response to miR-133a and miR-133b precursors transfection. Immunohistochemical staining results of tongue SCC tissues suggested that PKM2 was overexpressed in tongue SCC and was associated with the downregulation of miR-133a and miR-133b. Our results suggested that aberrant reduction of miR-133a and miR-133b was associated with the dysregulation of PKM2 in SCC of tongue. © 2008 Wiley-Liss, Inc.