Prognostic implications of micoRNA miR-195 expression in human tongue squamous cell carcinoma.

Prognostic implications of micoRNA miR-195 expression in human tongue squamous cell carcinoma.
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DOI:
10.1371/journal.pone.0056634
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Yu GY
Yu GY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jia LF;Wei SB;Gong K;Gan YH;Yu GY

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MIR-195在多种疾病中异常表达。但关于miR-195在舌鳞状细胞癌(TSCC)中的表达异常知之甚少。在本研究中,我们探讨了miR-195在舌鳞癌发生发展中的作用。应用定量逆转录聚合酶链式反应(qRT-PCR)检测81例TSCC组织中miR-195的表达。使用Kaplan-Meier曲线和对数等级检验以及Cox比例风险模型来检验这些患者的总体生存情况。用免疫组织化学方法检测已知的两个miR-195靶基因Cyclin D1和Bcl2在舌鳞癌组织中的表达。应用荧光激活细胞分选、荧光素酶报告基因检测和Western blotts检测miR-195过表达对TSCC细胞周期进程和细胞凋亡的影响,以及对细胞周期蛋白Cyclin D1和Bcl2表达的影响。MiR-195表达降低与肿瘤大小和临床分期有关。Kaplan-Meier生存分析表明,miR-195表达降低的TSCC患者总体生存率较低,在多因素分析中,miR-195表达水平低是影响该临床结果的独立预后因素。MiR-195的表达与Cyclin D1、Bcl2的表达呈负相关。在两株TSCC细胞中,miR-195过表达抑制了细胞周期进程,促进了细胞凋亡,降低了Cyclin D1和Bcl2的表达。MIR-195可能作为TSCC患者的预后指标具有潜在的应用价值。
miR-195 is aberrantly expressed in multiple types of disease. But little is known about the dysregulation of miR-195 in tongue squamous cell carcinoma (TSCC). In this study, we investigated the roles of miR-195 in the development and progression of TSCC. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we evaluated miR-195 expression in TSCC samples from 81 patients. Overall survival of these patients was examined using Kaplan–Meier curves with log-rank tests and the Cox proportional hazards model. The expression of two known miR-195 target genes, Cyclin D1 and Bcl-2, was also examined in the TSCC samples by immunohistochemistry. The effects of miR-195 overexpression on cell cycle progression and apoptosis and its effects on the expression of Cyclin D1 and Bcl-2 were examined in transfected TSCC cell lines (SCC-15 and Cal27) using fluorescence-activated cell sorting assays, luciferase reporter assays, and Western blots. Reduced miR-195 expression was associated with tumor size and the clinical stage of TSCC tumors. Kaplan–Meier survival analysis indicated that the TSCC patients with reduced expression of miR-195 had poor overall survival and in multivariable analyses low levels of miR-195 emerged as an independent prognostic factor for this clinical outcome. Levels of miR-195 expression were inversely correlated with the expression of Cyclin D1 and Bcl-2. Overexpression of miR-195 inhibited cell cycle progression, promoted apoptosis, and reduced Cyclin D1 and Bcl-2 expression in two TSCC cell lines. miR-195 may have potential applications as a prognostic factor for TSCC patients.
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