Wong Thian-Sze, Liu Xiao-Bing, Chung-Wai Ho Ambrose, Po-Wing Yuen Anthony, Wai-Man Ng Raymond, Ignace Wei William
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Int J Cancer. 2008 Jul 15;123(2):251-257. doi: 10.1002/ijc.23583.
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.
微小RNA（miRNA）是在基因表达中具有特定调控作用的非编码RNA。最近的报告表明它们参与了人类恶性肿瘤的发生。目前，关于miRNA在舌鳞状细胞癌（SCC）中的表达和功能尚无相关信息。在本研究中，我们使用基于Taqman的微小RNA检测方法评估了156种成熟miRNA在舌SCC中的表达模式。在这156种miRNA中，与配对的正常上皮细胞相比，miR-133a和miR-133b在舌SCC细胞中显著降低。用miR-133a和miR-133b前体转染的舌SCC细胞系显示增殖率降低。此外，引入前体后凋亡细胞数量增加。计算靶基因预测表明，miR-133a和miR-133b均靶向丙酮酸激酶M2型（PKM2）的转录本，PKM2是实体癌中的一种潜在癌基因。在舌SCC细胞系中，PKM2表达在转染miR-133a和miR-133b前体后降低。舌SCC组织的免疫组织化学染色结果表明，PKM2在舌SCC中过表达，并且与miR-133a和miR-133b的下调有关。我们的结果表明，miR-133a和miR-133b的异常降低与舌SCC中PKM2的失调有关。
