Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma.
Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma.
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DOI：
10.18632/oncotarget.709
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Kinoshita T;Hanazawa T;Nohata N;Kikkawa N;Enokida H;Yoshino H;Yamasaki T;Hidaka H;Nakagawa M;Okamoto Y;Seki N
最近我们的microRNA（miRNA）表达特征显示microRNA-218（miR-218）在癌组织中的表达降低，提示其可能是头颈部鳞状细胞癌（HNSCC）的肿瘤抑制因子。本研究旨在探讨miR-218及其介导的分子通路在HNSCC中的功能意义。癌细胞中miR-218的恢复导致HNSCC细胞系（FaDu和SAS）中细胞迁移和侵袭活性的显著抑制。对miR-218转染子的全基因组基因表达分析和计算机数据库分析表明，粘着斑途径是miR-218靶向途径的一个有希望的候选者。层粘连蛋白（laminins）是基底膜的一个重要的生物活性部分，其功能是多方面的，如影响细胞的分化、迁移和粘附，以及细胞的增殖和存活。有趣的是，层粘连蛋白-332的所有组分（LAMA 3、LAMB 3和LAMC 2）都被列为粘着斑途径的候选基因。此外，我们专注于具有miR-218靶位点的LAMB 3，基因表达研究和荧光素酶报告基因分析表明，LAMB 3直接受miR-218调控。沉默LAMB 3的研究表明显著抑制细胞迁移和侵袭。在具有HNSCC的临床样本中，与邻近的非癌组织相比，层粘连蛋白-332的表达水平在癌组织中显著上调。我们的分析数据表明，肿瘤抑制性miR-218通过调节粘着斑途径，特别是层粘连蛋白-332，促进癌细胞的迁移和侵袭。肿瘤抑制性miRNA介导的新的癌症途径为HNSCC肿瘤发生的潜在机制提供了新的见解。
Recent our microRNA (miRNA) expression signature revealed that expression of microRNA-218 (miR-218) was reduced in cancer tissues, suggesting a candidate of tumor suppressor in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the functional significance of miR-218 and its mediated moleculer pathways in HNSCC. Restoration of miR-218 in cancer cells led to significant inhibition of cell migration and invasion activities in HNSCC cell lines (FaDu and SAS). Genome-wide gene expression analysis of miR-218 transfectants and in silico database analysis showed that focal adhesion pathway was a promising candidate of miR-218 target pathways. The laminins are an important and biologically active part of the basal lamina, the function of that are various such as influencing cell differentiation, migration and adhesion as well as proliferation and cell survival. Interestingly, all components of laminin-332 (LAMA3, LAMB3 and LAMC2) are listed on the candidate genes in focal adhesion pathway. Furthermore, we focused on LAMB3 which has a miR-218 target site and gene expression studies and luciferase reporter assays showed that LAMB3 was directly regulated by miR-218. Silencing study of LAMB3 demonstrated significant inhibition of cell migration and invasion. In clinical specimens with HNSCC, the expression levels of laminin-332 were significantly upregulated in cancer tissues compared to adjacent non-cancerous tissues. Our analysis data showed that tumor suppressive miR-218 contributes to cancer cell migration and invasion through regulating focal adhesion pathway, especially laminin-332. Tumor suppressive miRNA-mediated novel cancer pathways provide new insights into the potential mechanisms of HNSCC oncogenesis.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1083/jcb.201102147
发表时间：
2012-02-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lu P;Weaver VM;Werb Z
通讯作者：
Werb Z
影响因子：
11.2
作者：
Alajez, Nehad M.;Lenarduzzi, Michelle;Liu, Fei-Fei
通讯作者：
Liu, Fei-Fei
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
6.4
作者：
Kano, Masayuki;Seki, Naohiko;Matsubara, Hisahiro
通讯作者：
Matsubara, Hisahiro