Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma
Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma
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DOI：
10.3892/ijo.2011.1096
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发表时间：
2011-11-01
影响因子：
5.2
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
--
作者：
Nohata, Nijiro;Hanazawa, Toyoyuki;Seki, Naohiko
基于我们对上颌窦鳞状细胞癌（MSSCC）的microRNA（miRNA）表达特征分析，我们发现miR-1和miR-133a在肿瘤组织中显著减少。实时荧光定量RT-PCR结果显示，与正常组织相比，miR-1和miR-133a在临床MSSCC组织中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，以及在MSSCC中由这些miRNA调控的新型癌症网络的鉴定。在癌细胞中下调的miRNAs（miR-1或miR-133a）的恢复揭示了这两种miRNAs显著抑制癌细胞增殖并诱导细胞凋亡。对这些miRNAs的分子靶点鉴定表明，transgelin 2（TAGLN 2）和嘌呤核苷磷酸化酶（PNP）受miR-1和miR-133a的调控。TAGLN 2和PNP mRNA表达水平在临床MSSCC肿瘤组织中均显著上调。靶基因的沉默研究表明，这两个基因抑制癌细胞增殖。新的miR-1/miR-133a调控的癌症通路的鉴定可以为MSSCC肿瘤发生的潜在分子机制提供新的见解。
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.