Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer.
Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer.
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DOI：
10.3892/ijo.2014.2752
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发表时间：
2015-02
影响因子：
5.2
通讯作者：
Enokida H
中科院分区：
文献类型：
--
作者：
Chiyomaru T;Seki N;Inoguchi S;Ishihara T;Mataki H;Matsushita R;Goto Y;Nishikawa R;Tatarano S;Itesako T;Nakagawa M;Enokida H
最近化疗药物治疗晚期膀胱癌(BC)的临床试验显示疗效有限。因此，需要新的预后标记物和更有效的治疗策略。实现这些目标的一种方法是通过分析RNA网络。我们最近对microRNA(MiRNA)表达特征的研究表明，microRNA-23b/27b(miR-23b/27b)簇在各种类型的人类癌症中经常下调。然而，miR-23b/27b簇在BC细胞中的功能作用仍不清楚。因此，本研究的目的是研究miR-23b/27b簇及其调控的分子靶点的功能意义，重点是它在BC的发生和转移中的作用。在BC临床标本中miR-23b/27b簇的表达水平显著降低。修复成熟的miR-23b或miR-27b miRNAs显著抑制癌细胞的迁移和侵袭，表明这些聚集的miRNAs作为肿瘤抑制因子发挥作用。基因表达数据和电子计算机分析表明，编码表皮生长因子受体(EGFR)和肝细胞生长因子受体(c-Met)的基因是miR-23b/27b簇的潜在靶点。荧光素酶报告分析和Western blotting表明，EGFR和c-Met受体类胰氨酸激酶直接受这些聚集性miRNAs的调控。我们的结论是，抑制肿瘤的miR-23b/27b簇的表达降低，通过直接调节EGFR和c-Met信号通路，促进了癌细胞在BC中的增殖、迁移和侵袭。我们关于抑制肿瘤的miR-23b/27b调控的RNA网络的数据为研究BC的肿瘤发生和转移的潜在机制提供了新的见解。
Recent clinical trials of chemotherapeutics for advanced bladder cancer (BC) have shown limited benefits. Therefore, new prognostic markers and more effective treatment strategies are required. One approach to achieve these goals is through the analysis of RNA networks. Our recent studies of microRNA (miRNA) expression signatures revealed that the microRNA-23b/27b (miR-23b/27b) cluster is frequently downregulated in various types of human cancers. However, the functional role of the miR-23b/27b cluster in BC cells is still unknown. Thus, the aim of the present study was to investigate the functional significance of the miR-23b/27b cluster and its regulated molecular targets, with an emphasis on its contributions to BC oncogenesis and metastasis. The expression levels of the miR-23b/27b cluster were significantly reduced in BC clinical specimens. Restoration of mature miR-23b or miR-27b miRNAs significantly inhibited cancer cell migration and invasion, suggesting that these clustered miRNAs function as tumor suppressors. Gene expression data and in silico analysis demonstrated that the genes coding for the epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met) were potential targets of the miR-23b/27b cluster. Luciferase reporter assays and western blotting demonstrated that EGFR and c-Met receptor trypsine kinases were directly regulated by these clustered miRNAs. We conclude that the decreased expression of the tumor-suppressive miR-23b/27b cluster enhanced cancer cell proliferation, migration and invasion in BC through direct regulation of EGFR and c-Met signaling pathways. Our data on RNA networks regulated by tumor-suppressive miR-23b/27b provide new insights into the potential mechanisms of BC oncogenesis and metastasis.
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影响因子：
8.8
作者：
Kojima, S.;Chiyomaru, T.;Kawakami, K.;Yoshino, H.;Enokida, H.;Nohata, N.;Fuse, M.;Ichikawa, T.;Naya, Y.;Nakagawa, M.;Seki, N.
通讯作者：
Seki, N.
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Chiyomaru T;Yamamura S;Fukuhara S;Hidaka H;Majid S;Saini S;Arora S;Deng G;Shahryari V;Chang I;Tanaka Y;Tabatabai ZL;Enokida H;Seki N;Nakagawa M;Dahiya R
通讯作者：
Dahiya R
肿瘤抑制的microRNA-29s通过靶向头部和颈部鳞状细胞癌中的层粘连蛋白 - 整合蛋白信号传导来抑制癌细胞的迁移和侵袭。
影响因子：
8.8
作者：
Kinoshita, T.;Nohata, N.;Hanazawa, T.;Kikkawa, N.;Yamamoto, N.;Yoshino, H.;Itesako, T.;Enokida, H.;Nakagawa, M.;Okamoto, Y.;Seki, N.
通讯作者：
Seki, N.
影响因子：
11.2
作者：
Kefas, Benjamin;Godlewski, Jakub;Purow, Benjamin
通讯作者：
Purow, Benjamin