Ye Wenwei, Xue Jisen, Zhang Qian, Li Fuyao, Zhang Wei, Chen Huijun, Huang Yibo, Zheng Feiyun
Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Rep. 2014 Sep;32(3):1193-9. doi: 10.3892/or.2014.3303. Epub 2014 Jul 3.
Accumulating evidence has demonstrated that microRNAs (miRNAs) play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. The role of microRNA-449a (miR-449a) in endometrial cancer remains unclear. We examined the levels of miR-449a and miR-449b in benign endometrium, type I and type II endometrial cancer tissues by quantitative real-time polymerase chain reaction. To further investigate the roles of miR-449a in regulating the behavior of endometrial cancer cells, we overexpressed miR-449a in the endometrial cancer cell line HEC-1B, which had low endogenous miR-449a expression. We analyzed the effects of miR-449a overexpression on CDC25 expression, proliferation, invasion and apoptosis of HEC-1B cells. We found that miR-449a and miR-449b levels were markedly reduced in type II endometrial cancer tissues but not in type I endometrial cancer tissues compared with normal endometrium. Overexpression of miR-449a significantly inhibited the proliferation, invasion and clonogenic survival of HEC-1B cells. MiR-449a overexpression also induced apoptosis in HEC-1B cells. In addition, real-time RT-PCR and western blot analysis showed that CDC25A expression was suppressed by miR-449a overexpression. Our results suggest that miR-449a may act as a tumor suppressor by targeting CDC25A in endometrial cancer.
越来越多的证据表明,微小RNA(miRNA)通过作为癌基因或肿瘤抑制因子发挥作用,在癌症的发生和发展中起关键作用。微小RNA-449a(miR-449a)在子宫内膜癌中的作用仍不清楚。我们通过定量实时聚合酶链反应检测了良性子宫内膜、I型和II型子宫内膜癌组织中miR-449a和miR-449b的水平。为了进一步研究miR-449a在调节子宫内膜癌细胞行为中的作用,我们在低内源性miR-449a表达的子宫内膜癌细胞系HEC-1B中过表达miR-449a。我们分析了miR-449a过表达对HEC-1B细胞CDC25表达、增殖、侵袭和凋亡的影响。我们发现,与正常子宫内膜相比,II型子宫内膜癌组织中miR-449a和miR-449b水平明显降低,而I型子宫内膜癌组织中则没有。miR-449a的过表达显著抑制了HEC-1B细胞的增殖、侵袭和克隆存活。miR-449a的过表达还诱导了HEC-1B细胞的凋亡。此外,实时RT-PCR和蛋白质印迹分析表明,miR-449a的过表达抑制了CDC25A的表达。我们的结果表明,miR-449a可能通过靶向子宫内膜癌中的CDC25A发挥肿瘤抑制作用。