Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Br J Cancer. 2011 Mar 1;104(5):808-18. doi: 10.1038/bjc.2011.23. Epub 2011 Feb 8.
On the base of the microRNA (miRNA) expression signature of bladder cancer (BC), we found that miR-1 and miR-133a were significantly downregulated in BC. In this study, we focussed on the functional significance of miR-1 and miR-133a in BC cell lines and identified a molecular network of these miRNAs.
We investigated the miRNA expression signature of BC clinical specimens and identified several downregulated miRNAs (miR-133a, miR-204, miR-1, miR-139-5p, and miR-370). MiR-1 and miR-133a showed potential role of tumour suppressors by functional analyses of BC cells such as cell proliferation, apoptosis, migration, and invasion assays. Molecular target searches of these miRNAs showed that transgelin 2 (TAGLN2) was directly regulated by both miR-1 and miR-133a. Silencing of TAGLN2 study demonstrated significant inhibitions of cell proliferation and increase of apoptosis in BC cell lines. The immunohistochemistry showed a positive correlation between TAGLN2 expression and tumour grade in clinical BC specimens.
The downregulation of miR-1 and miR-133a was a frequent event in BC, and these miRNAs were recognised as tumour suppressive. TAGLN2 may be a target of both miRNAs and had a potential oncogenic function. Therefore, novel molecular networks provided by miRNAs may provide new insights into the underlying molecular mechanisms of BC.
在膀胱癌（BC）的 microRNA（miRNA）表达特征的基础上，我们发现 miR-1 和 miR-133a 在 BC 中显著下调。在这项研究中，我们专注于 miR-1 和 miR-133a 在 BC 细胞系中的功能意义，并确定了这些 miRNA 的分子网络。
我们研究了 BC 临床标本的 miRNA 表达特征，确定了几个下调的 miRNA（miR-133a、miR-204、miR-1、miR-139-5p 和 miR-370）。miR-1 和 miR-133a 通过 BC 细胞的功能分析（如细胞增殖、凋亡、迁移和侵袭测定）显示出肿瘤抑制因子的潜在作用。这些 miRNA 的分子靶标搜索表明，转凝胶蛋白 2（TAGLN2）被 miR-1 和 miR-133a 直接调控。TAGLN2 沉默研究表明，BC 细胞系中的细胞增殖受到显著抑制，凋亡增加。免疫组织化学显示，临床 BC 标本中 TAGLN2 表达与肿瘤分级呈正相关。
miR-1 和 miR-133a 的下调在 BC 中是一个常见事件，这些 miRNA 被认为是肿瘤抑制因子。TAGLN2 可能是这两个 miRNA 的靶点，具有潜在的致癌功能。因此，miRNA 提供的新分子网络可能为 BC 的潜在分子机制提供新的见解。
