Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC)
Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC)
复制标题
DOI：
10.1038/jhg.2011.66
复制
发表时间：
2011-08-01
影响因子：
3.5
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
--
作者：
Nohata, Nijiro;Hanazawa, Toyoyuki;Seki, Naohiko
我们的microRNA(MiRNA)在下咽鳞状细胞癌、上颌窦鳞状细胞癌和食管鳞癌组织中的表达特征表明，与正常上皮相比，miR-375在癌组织中的表达显著降低。在本研究中，我们重点研究miR-375在癌细胞中的功能意义以及在头颈部鳞状细胞癌(HNSCC)中发现miR-375调控的新的癌网络。修复miR-375可显著抑制SAS和FaDu细胞的增殖和诱导细胞凋亡，提示miR-375具有肿瘤抑制作用。我们采用全基因组基因表达分析来寻找miR-375调控的分子靶点。基因表达数据和荧光素酶报告分析表明，AEG-1/MTDH受到miR-375的直接调控。转染siAEG-1/mTdH的HNSCC细胞的癌细胞增殖受到明显抑制。此外，AEG-1/MTDH在癌组织中的表达水平显著上调。因此，AEG-1/MTDH可能作为癌基因在HNSCC中发挥作用。新的抑癌miRNA及其调控的肿瘤通路的发现将为深入研究HNSCC的致癌分子机制提供新的思路。《人类遗传学杂志》(2011年)56595601；DOI：10.1038/jhg.2011.66；2011年7月14日在线发布
Our microRNA (miRNA) expression signatures of hypopharyngeal squamous cell carcinoma, maxillary sinus squamous cell carcinoma and esophageal squamous cell carcinoma revealed that miR-375 was significantly reduced in cancer tissues compared with normal epithelium. In this study, we focused on the functional significance of miR-375 in cancer cells and identification of miR-375-regulated novel cancer networks in head and neck squamous cell carcinoma (HNSCC). Restoration of miR-375 showed significant inhibition of cell proliferation and induction of cell apoptosis in SAS and FaDu cell lines, suggesting that miR-375 functions as a tumor suppressor. We adopted genome-wide gene expression analysis to search for miR-375-regulated molecular targets. Gene expression data and luciferase reporter assays revealed that AEG-1/MTDH was directly regulated by miR-375. Cancer cell proliferation was significantly inhibited in HNSCC cells transfected with si-AEG-1/MTDH. In addition, expression levels of AEG-1/MTDH were significantly upregulated in cancer tissues. Therefore, AEG-1/MTDH may function as an oncogene in HNSCC. The identification of novel tumor suppressive miRNA and its regulated cancer pathways could provide new insights into potential molecular mechanisms of HNSCC oncogenesis. Journal of Human Genetics (2011) 56, 595-601; doi:10.1038/jhg.2011.66; published online 14 July 2011