MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways.

MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways.
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DOI:
10.1038/bjc.2015.19
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发表时间:
2015-03-03
影响因子:
8.8
通讯作者:
Seki, N.
Seki, N.
中科院分区:
医学1区
文献类型:
--
作者:
Fukumoto, I.;Hanazawa, T.;Kinoshita, T.;Kikkawa, N.;Koshizuka, K.;Goto, Y.;Nishikawa, R.;Chiyomaru, T.;Enokida, H.;Nakagawa, M.;Okamoto, Y.;Seki, N.

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microRNA(miRNAs)在多种癌症的发生中起重要作用。本研究旨在检测口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中miR-26 a和miR-26 b的表达特征,并探讨其在OSCC中的功能作用。通过基于PCR的阵列方法构建OSCC miRNA标签。对差异表达的miRNAs进行功能研究,以研究OSCC细胞的细胞增殖、迁移和侵袭。进行计算机数据库和全基因组基因表达分析以鉴定miR-26 a/B介导的分子靶点和途径。miR-26 a和miR-26 b在口腔鳞癌中表达显著下调。miR-26 a和miR-26 b在癌细胞系中的恢复揭示了这些miRNA显著抑制癌细胞迁移和侵袭。我们的数据表明,新的跨膜TMEM 184 B基因是miR-26 a/B调控的直接靶点。沉默TMEM 184 B基因可抑制癌细胞的迁移和侵袭,并对肌动蛋白细胞毒通路相关基因进行调控。肿瘤抑制性miR-26 a/B的缺失通过直接调节TMEM 184 B增强了OSCC中癌细胞的迁移和侵袭。我们的数据描述了由肿瘤抑制性miR-26 a/B调控的途径,为OSCC肿瘤发生和转移的潜在机制提供了新的见解。
MicroRNAs (miRNAs) have been shown to play major roles in carcinogenesis in a variety of cancers. The aim of this study was to determine the miRNA expression signature of oral squamous cell carcinoma (OSCC) and to investigate the functional roles of miR-26a and miR-26b in OSCC cells. An OSCC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were performed to investigate cell proliferation, migration, and invasion in OSCC cells. In silico database and genome-wide gene expression analyses were performed to identify molecular targets and pathways mediated by miR-26a/b. miR-26a and miR-26b were significantly downregulated in OSCC. Restoration of both miR-26a and miR-26b in cancer cell lines revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our data demonstrated that the novel transmembrane TMEM184B gene was a direct target of miR-26a/b regulation. Silencing of TMEM184B inhibited cancer cell migration and invasion, and regulated the actin cytoskeleton-pathway related genes. Loss of tumour-suppressive miR-26a/b enhanced cancer cell migration and invasion in OSCC through direct regulation of TMEM184B. Our data describing pathways regulated by tumour-suppressive miR-26a/b provide new insights into the potential mechanisms of OSCC oncogenesis and metastasis.
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。
DOI: 10.1038/bjc.2013.607
发表时间: 2013-11-12
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.
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DOI: 10.1371/journal.pone.0072662
发表时间: 2013
期刊: PloS one
影响因子: 3.7
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DOI: 10.1158/1078-0432.ccr-11-1944
发表时间: 2011-11-15
期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子: --
作者:
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DOI: 10.18632/oncotarget.709
发表时间: 2012-11
期刊: Oncotarget
影响因子: --
作者:
Kinoshita T;Hanazawa T;Nohata N;Kikkawa N;Enokida H;Yoshino H;Yamasaki T;Hidaka H;Nakagawa M;Okamoto Y;Seki N
通讯作者: Seki N
DOI: 10.1002/ijc.28667
发表时间: 2014-11-15
影响因子: 6.4
作者:
Jia, Ling-Fei;Wei, Su-Bi;Yu, Guang-Yan
通讯作者: Yu, Guang-Yan