Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma.
Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma.
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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
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发表时间：
2013-11-12
影响因子：
8.8
通讯作者：
Seki, N.
中科院分区：
文献类型：
--
作者：
Kinoshita, T.;Nohata, N.;Hanazawa, T.;Kikkawa, N.;Yamamoto, N.;Yoshino, H.;Itesako, T.;Enokida, H.;Nakagawa, M.;Okamoto, Y.;Seki, N.
我们最近对microRNA(MiRNA)表达特征的研究表明，microRNA-29s(miR-29s；miR-29a/b/c)在头颈部鳞状细胞癌(HNSCC)中显著下调，在人类癌症中可能是肿瘤抑制的miRNAs。本研究的目的是探讨miR-29S在肿瘤细胞中的功能意义，寻找miR-29S介导的新的肿瘤通路和与HNSCC发生和转移相关的基因。使用成熟的miR-29细胞进行功能获得研究，研究两种HNSCC细胞系(SAS和FaDu)的细胞增殖、迁移和侵袭。为了确定miR-29S介导的分子途径和靶点，我们利用了基因表达分析和电子数据库分析。采用功能缺失分析研究miR-29S靶基因的功能意义。在SAS和FaDu细胞系中修复miR-29s可显著抑制癌细胞的迁移和侵袭。基因表达数据和电子计算机分析表明，miR-29S调节焦点黏附途径。此外，层粘连蛋白γ2(LAMC2)和α6整合素(ITGA6)基因是miR-29S调控的候选靶点。荧光素酶报告分析表明miR-29S直接调控LAMC2和ITGA6。沉默LAMC2和ITGA6基因显著抑制癌细胞的迁移和侵袭。MiR-29的下调是HNSCC的常见事件。MiR-29作为肿瘤抑制因子，直接靶向层粘连蛋白-整合素信号通路。对抑制肿瘤的miRNA介导的癌症途径的认识为深入了解HNSCC的肿瘤发生和转移的潜在机制提供了新的见解，并为该疾病提供了新的治疗策略。
Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-29s (miR-29s; miR-29a/b/c) were significantly downregulated in head and neck squamous cell carcinoma (HNSCC) and were putative tumour-suppressive miRNAs in human cancers. Our aim in this study was to investigate the functional significance of miR-29s in cancer cells and to identify novel miR-29s-mediated cancer pathways and responsible genes in HNSCC oncogenesis and metastasis. Gain-of-function studies using mature miR-29s were performed to investigate cell proliferation, migration and invasion in two HNSCC cell lines (SAS and FaDu). To identify miR-29s-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-29s target genes. Restoration of miR-29s in SAS and FaDu cell lines revealed significant inhibition of cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that miR-29s modulated the focal adhesion pathway. Moreover, laminin γ2 (LAMC2) and α6 integrin (ITGA6) genes were candidate targets of the regulation of miR-29s. Luciferase reporter assays showed that miR-29s directly regulated LAMC2 and ITGA6. Silencing of LAMC2 and ITGA6 genes significantly inhibited cell migration and invasion in cancer cells. Downregulation of miR-29s was a frequent event in HNSCC. The miR-29s acted as tumour suppressors and directly targeted laminin–integrin signalling. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and metastasis and suggests novel therapeutic strategies for the disease.
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DOI：
10.1084/jem.20090831
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Han YC;Park CY;Bhagat G;Zhang J;Wang Y;Fan JB;Liu M;Zou Y;Weissman IL;Gu H
通讯作者：
Gu H
DOI：
10.1158/1078-0432.ccr-08-3131
发表时间：
2009-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Avissar M;Christensen BC;Kelsey KT;Marsit CJ
通讯作者：
Marsit CJ
影响因子：
8.8
作者：
通讯作者：
--
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
影响因子：
3.7
作者：
Falcioni, R;Antonini, A;Sacchi, A
通讯作者：
Sacchi, A