miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma.

miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma.
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DOI:
10.18632/oncotarget.213
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发表时间:
2011-01
期刊:
影响因子:
--
通讯作者:
Seki N
Seki N
中科院分区:
其他
文献类型:
--
作者:
Nohata N;Sone Y;Hanazawa T;Fuse M;Kikkawa N;Yoshino H;Chiyomaru T;Kawakami K;Enokida H;Nakagawa M;Shozu M;Okamoto Y;Seki N

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基于下咽癌和食管鳞状细胞癌的微小RNA(miRNA)表达特征,我们发现癌细胞中miR-1显着下调。在这项研究中,我们研究了miR-1在头颈部鳞状细胞癌(HNSCC)细胞中的功能意义,并确定了miR-1调节的新癌症途径。使用miR-1的功能获得研究显示HNSCC细胞增殖、侵袭和迁移显著降低。此外,在癌细胞的miR-1转染后,证实了细胞凋亡和细胞周期停滞的促进。对miR-1靶点的研究表明,transgelin 2(TAGLN 2)直接受miR-1调控。TAGLN 2的沉默显著抑制HNSCC细胞中的细胞增殖和侵袭。在HNSCC临床标本中证实了miR-1的下调和TAGLN 2的上调。我们的数据表明,TAGLN 2可能具有致癌功能,并可能受到miR-1(HNSCC中的肿瘤抑制性miRNA)的调控。新的miR-1调控的癌症通路的鉴定可以为HNSCC致癌的潜在分子机制提供新的见解。
Based on the microRNA (miRNA) expression signatures of hypopharyngeal and esophageal squamous cell carcinoma, we found that miR-1 was significantly down-regulated in cancer cells. In this study, we investigated the functional significance of miR-1 in head and neck squamous cell carcinoma (HNSCC) cells and identified miR-1-regulated novel cancer pathways. Gain-of-function studies using miR-1 revealed significant decreases in HNSCC cell proliferation, invasion, and migration. In addition, the promotion of cell apoptosis and cell cycle arrest was demonstrated following miR-1 transfection of cancer cells. A search for the targets of miR-1 revealed that transgelin 2 (TAGLN2) was directly regulated by miR-1. Silencing of TAGLN2 significantly inhibited cell proliferation and invasion in HNSCC cells. Down-regulation of miR-1 and up-regulation of TAGLN2 were confirmed in HNSCC clinical specimens. Our data indicate that TAGLN2 may have an oncogenic function and may be regulated by miR-1, a tumor suppressive miRNA in HNSCC. The identification of novel miR-1-regulated cancer pathways could provide new insights into potential molecular mechanisms of HNSCC carcinogenesis.