Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas.
Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas.
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DOI：
10.1016/j.oraloncology.2011.11.006
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发表时间：
2012-01
期刊：
影响因子：
4.8
通讯作者：
Lu, Shi-Long
中科院分区：
文献类型：
--
作者：
Minor, Jacob;Wang, Xiaotian;Zhang, Fang;Song, John;Jimeno, Antonio;Wang, Xiao-Jing;Lu, Xian;Gross, Neil;Kulesz-Martin, Molly;Wang, Daren;Lu, Shi-Long
DNA甲基化检测作为头颈部鳞状细胞癌（HNSCC）的生物标志物已经产生了有希望的结果。然而，目前的研究小组受到敏感和特异性肿瘤标志物数量不足的限制。MicroRNAs （miR）在肿瘤发生中起着重要作用，可能代表了一组新的癌症生物标志物。我们研究了107人头颈部组织样本和对照组中miR-9的三个miRNA启动子位点（miR-9-1, miR-9-2, miR-9-3）的甲基化。我们发现miR-9-1和miR-9-3的甲基化在口腔癌和口咽癌中比在喉癌中更高，这两种肿瘤类型的总敏感性分别为63%和56%，而喉癌的总敏感性为21%。miR-9的定量PCR显示，肿瘤组织中miR-9的甲基化表达降低。为了研究miR-9甲基化的功能后果，我们发现miR-9甲基化与人HNSCC细胞系中miR-9的表达水平相关。使用5-aza-脱氧胞苷进行去甲基化处理，恢复了miR-9甲基化的人HNSCC细胞系UM-SCC22A中的表达。此外，转染miR-9到UM-SCC22A细胞系后，细胞增殖和活力明显受到抑制，而PTEN的表达升高。总之，我们的研究结果表明，miR-9-1和miR-9-3的甲基化是HNSCC的敏感和特异性生物标志物，特别是对于口腔和口咽鳞状细胞癌。此外，miR-9可能通过抑制细胞增殖和肿瘤抑制因子PTEN的升高在HNSCC中发挥抑癌作用。
Detection of DNA methylation has produced promising results as biomarkers for head and neck squamous cell carcinoma (HNSCC). However, current panels are limited by an insufficient number of sensitive and specific tumor markers. MicroRNAs (miR) play an important role in tumorigenesis, and may represent a novel panel of molecules for the development of cancer biomarkers. We investigated methylation of three miRNA promoter sites of miR-9 (miR-9-1, miR-9-2, miR-9-3) in 107 human head and neck tissue samples and controls. We found methylations of miR-9-1 and miR-9-3 were higher in oral and oropharyngeal carcinomas than that in laryngeal carcinoma, achieving a combined sensitivity of 63% and 56%, respectively, for these two tumor types, compared to 21% for the laryngeal carcinoma. Quantitative PCR of miR-9 showed reduced expression associated with methylation of miR-9 in tumor tissues. To investigate the functional consequences of miR-9 methylation, we found that miR-9 methylation is correlated with miR-9 expression level in human HNSCC cell lines. Demethylation treatment using 5-aza-deoxycytidine restored its expression in a miR-9 methylated human HNSCC cell line UM-SCC22A. Furthermore, cell proliferation and viability was significantly inhibited, while PTEN expression was elevated after transfection of miR-9 into the UM-SCC22A cell line. In summary, our results suggest that methylations of miR-9-1 and miR-9-3 are sensitive and specific biomarkers for HNSCC, particularly for oral and oropharyngeal squamous cell carcinomas. In addition, miR-9 may function as a tumor suppressor in HNSCC through inhibition of cell proliferation and elevation of tumor suppressor PTEN.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
DOI：
10.1111/j.1750-3639.2008.00184.x
发表时间：
2009-07
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Nass D;Rosenwald S;Meiri E;Gilad S;Tabibian-Keissar H;Schlosberg A;Kuker H;Sion-Vardy N;Tobar A;Kharenko O;Sitbon E;Lithwick Yanai G;Elyakim E;Cholakh H;Gibori H;Spector Y;Bentwich Z;Barshack I;Rosenfeld N
通讯作者：
Rosenfeld N
影响因子：
11.2
作者：
Hsu PY;Deatherage DE;Rodriguez BA;Liyanarachchi S;Weng YI;Zuo T;Liu J;Cheng AS;Huang TH
通讯作者：
Huang TH
影响因子：
7.3
作者：
Lehmann, U.;Hasemeier, B.;Kreipe, H.
通讯作者：
Kreipe, H.
影响因子：
8
作者：
Hildebrandt, M. A. T.;Gu, J.;Wu, X.
通讯作者：
Wu, X.