miR-34a通过靶向抗凋亡基因Survivin抑制皮肤鳞状细胞癌增殖的研究

miR-34a affect the proliferation of squamous cell carcinoma by targeting Survivin

关键词:  皮肤鳞状细胞癌  miR-34a  Survivin  增殖

Key words:  squamous cell carcinoma  miR-34a  Survivin  proliferation

摘要:

目的　研究miR-34a在皮肤鳞状细胞癌(SCC)中的表达及对肿瘤细胞增殖、抗凋亡的调控作用及机制。　方法　采用实时定量PCR检测46例SCC病人肿瘤组织及15例正常皮肤组织中miR-34a及Survivin的表达；将miR-34a mimic转染进皮肤鳞状细胞癌A431细胞系，探讨miR-34a对SCC细胞增殖、Survivin表达的影响；评估miR-34a及Survivin表达对SCC预后的生物诊断价值。 　结果　　（1）低分化SCC患者miR-34a显著低于高分化组，而Survivin则显著高于高分化组（P均<0.05）。与正常皮肤比较，SCC病人的miR-34a显著降低，而Survivin表达则显著提高，P值分别为0.0013及<0.0001，差异均有极显著性意义。（2）与未转染组相比，miR-34a mimic可以显著抑制A431细胞增殖（P<0.05）；同时显著降低Survivin蛋白表达（P<0.01）。（3）高miR-34a表达的SCC患者生存率显著高于低表达者，P=0.020567；高Survivin表达的SCC患者生存率则显著低于高表达者，P=0.008198。　结论　　miR-34a可通过对Survivin表达调控影响SCC细胞增殖，同时它也可作为一个很好的生物学诊断指标为评估SCC病人预后提供参考。

Abstract:

Objective To analyze the relationship between miR-34a and Survivin in proliferation of cutaneous squamous cell carcinoma (SCC). Methods miR-34a and Survivin expression in SCC tissues were detected by quantitative real-time polymerase chain reaction. miR-34a mimic was transfected into SCC cell line A431 to increase its level. The effects of miR-34a on cell proliferation and Survivin expression were tested by MTS, semi-RT-PCR and western blotting analyses. Results The expression of miR-34a was significantly lower in SCC tissue than that in normal tissue, and lower in low differentiation SCC than that in high differentiation SCC. Survivin expression was higher in SCC tissue than that in normal tissue, and higher in low differentiation SCC than that in high differentiation SCC. The miR-34a expression was positively correlated with histologic differentiation and negatively correlated with Survivin expression. The transfection of miR-34a mimic significantly suppressed cell proliferation and decreased Survivin protein expression, but did not affect Survivin mRNA expression level. SCC patients with miR-34a high expression and Survivin low expression have a better prognosis. Conclusion miR-34a could affect the occurrence of SCC by targeting antiapoptotic gene Survivin.