miR-99a对口腔鳞癌增殖能力的影响

MiR-99a inhibits proliferation of oral squamous cell carcinoma by targeting mTOR pathway

目的:探讨miR-99a在口腔鳞状细胞中的表达及对口腔鳞癌细胞生物学行为的影响。方法:检索GEO数据库中与口腔鳞癌相关的miRNA芯片进行二次分析。检测63例口腔鳞癌组织和口腔鳞癌细胞株内miR-99a的表达,分析其与临床病理指标及患者预后之间的关系。上调miR-99a的表达,检测其对口腔鳞癌细胞生长和克隆形成的影响,并通过Targetscan等软件预测其靶基因。采用SPSS 19.0软件包对数据进行统计学分析。结果:GSE103931芯片显示,miR-99a在口腔鳞癌中下调最显著,且miR-99a也在口腔鳞癌细胞株内显著低表达。miR-99a的表达与患者T分期、病理分级和预后密切相关。上调miR-99a的表达可抑制口腔鳞癌细胞增殖;而抑制miR-99a的表达,则促进口腔鳞癌细胞增殖。通过Targetscan等软件发现,mTOR是miR-99a的靶基因,且与miR-99a的表达呈负相关。结论:miR-99a在口腔鳞癌组织和细胞系中低表达。上调miR-99a能抑制口腔鳞癌细胞株SCC25和SCC9的增殖能力,其机制是通过调控mTOR的表达而实现。

PURPOSE:To investigate miR-99 a expression and its effect on proliferation of oral squamous cell carcinoma(OSCC).METHODS:miRNA microarrays associated with OSCC were identified in GEO database.The expression levels of miR-99 a were detected in 63 OSCC tissues and adjacent normal tissues and cell lines.The relationship between clinicopathological parameters and miR-99 a expression was analyzed by using ANOVA analysis.The ability of cell growth and clone formation were examined in SCC9 and SCC25 cells transfected with miR-99 a mimics.The target genes of miR-99 a were predicted by Targetscan software.There resulting data were analyzed using SPSS 19.0 software package.RESULTS:The differently expressed miRNAs were analyzed based on GSE103931 microarray.miR-99 a was significantly downregulated in OSCC tissues and cell lines.miR-99 a expression was significantly associated with T stage,pathological grading and patients’prognosis.miR-99 a overexpression inhibited OSCC cell proliferation and clone formation,while miR-99 a inhibition contributed to decreased proliferation and clone formation ability.In addition,miR-99 a combined with mTOR gene’s 3’UTR was negatively correlated with mTOR expression in OSCC tissues.CONCLUSIONS:miR-99 a functions as a tumor suppressor in OSCC and inhibits OSCC cell proliferation by targeting mTOR.