Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma
Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma
复制标题
DOI：
10.1002/ijc.28667
复制
发表时间：
2014-11-15
影响因子：
6.4
通讯作者：
Yu, Guang-Yan
中科院分区：
文献类型：
--
作者：
Jia, Ling-Fei;Wei, Su-Bi;Yu, Guang-Yan
microRNA miR-26 a和长链非编码RNA（lncRNA）MEG 3基因已被独立报道为多种癌症的肿瘤抑制基因，但两者均未与舌鳞状细胞癌（TSCC）相关。我们在此报告，miR-26 a和lncRNA MEG 3基因表达在TSCC中均显著降低，与匹配的非恶性组织中的水平相比，miR-26 a和MEG 3的联合低表达水平成为TSCC患者临床预后不良的独立预后因素。在人TSCC细胞系SCC-15和CAL 27中的测定显示，miR-26 a靶向DNA甲基转移酶3B转录物，并且其抑制可能导致MEG 3的上调，从而在TSCC组织中观察到的miR-26 a和MEG 3减少之间提供了合理的联系。此外，miR-26 a和MEG 3在SCC-15和CAL 27细胞中的过表达可抑制细胞增殖和细胞周期进程，并促进细胞凋亡。考虑到与miR-26 a和MEG 3减少相关的不良预后结果，我们的研究结果表明，这些因素可能在TSCC发病机制中发挥重要的抗肿瘤作用。此外，它们代表了TSCC患者分层的潜在预后生物标志物。
MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR-26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.