Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Int J Oncol. 2011 Nov;39(5):1099-107. doi: 10.3892/ijo.2011.1096. Epub 2011 Jun 23.
Based on our microRNA (miRNA) expression signature analysis of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-1 and miR-133a were significantly reduced in tumor tissues. Quantitative real-time RT-PCR revealed that the expression levels of miR-1 and miR-133a were significantly downregulated in clinical MSSCC tumor tissues compared with normal tissues. We focused on the functional significance of miR-1 and miR-133a in cancer cells and identification of the novel cancer networks regulated by these miRNAs in MSSCC. Restoration of downregulated miRNAs (miR-1 or miR-133a) in cancer cells revealed that both miRNAs significantly inhibited cancer cell proliferation and induced cell apoptosis. Molecular target identification of these miRNAs showed that transgelin 2 (TAGLN2) and purine nucleoside phosphorylase (PNP) were regulated by miR-1 and miR-133a. Both TAGLN2 and PNP mRNA expression levels were significantly upregulated in clinical MSSCC tumor tissues. Silencing studies of target genes demonstrated that both genes inhibited cancer cell proliferation. The identification of novel miR-1/miR-133a-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.
基于我们对上颌窦鳞状细胞癌 (MSSCC) 的 microRNA (miRNA) 表达谱分析，我们发现肿瘤组织中 miR-1 和 miR-133a 的表达明显降低。实时定量 RT-PCR 显示，与正常组织相比，临床 MSSCC 肿瘤组织中 miR-1 和 miR-133a 的表达水平显著下调。我们专注于 miR-1 和 miR-133a 在癌细胞中的功能意义，以及鉴定这些 miRNA 在 MSSCC 中调控的新型癌症网络。在癌细胞中恢复下调的 miRNA（miR-1 或 miR-133a）后，发现这两种 miRNA 均能显著抑制癌细胞增殖并诱导细胞凋亡。这些 miRNA 的分子靶标鉴定表明，转胶蛋白 2 (TAGLN2) 和嘌呤核苷磷酸化酶 (PNP) 受 miR-1 和 miR-133a 的调控。在临床 MSSCC 肿瘤组织中，TAGLN2 和 PNP 的 mRNA 表达水平均显著上调。靶基因的沉默研究表明，这两个基因均能抑制癌细胞增殖。鉴定新型 miR-1/miR-133a 调控的癌症通路可为 MSSCC 肿瘤发生的潜在分子机制提供新的见解。
