Zhang Wei, Zeng Qingru, Ban Zhenying, Cao Jing, Chu Tianjiao, Lei Dongmei, Liu Chi, Guo Wentao, Zeng Xianxu
Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Ultrasound, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Oncol Lett. 2018 Nov;16(5):5543-5550. doi: 10.3892/ol.2018.9327. Epub 2018 Aug 20.
MicroRNAs serve a role in the development of ovarian cancer (OC). The present study investigated whether let-7c is able to regulate the proliferation of OC cells by targeting cell division cycle 25A (CDC25a). The reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of let-7c in OC specimens. Let-7c agomir was transfected into OC cells, and the proliferation and apoptosis of OC cells were detected. A dual-luciferase assay and western blotting were performed to analyze whether CDC25a was the target gene of let-7c as well as its interaction site. The results revealed that, in OC tissue, let-7c was downregulated when compared with normal ovarian tissue. A Cell Counting Kit-8 (CCK8) assay, colony formation assay and flow cytometry demonstrated that increased expression of let-7c was able to inhibit the proliferation and increase the apoptosis of OC cells. Western blotting revealed that upregulated let-7c is able to decrease the expression of CDC25a, and a dual-luciferase assay and a recovery assay demonstrated that let-7c was able to regulate the expression of the 3' untranslated region of CDC25a. Therefore, the roles of let-7c in inhibiting the proliferation and promoting the apoptosis of OC cells may be realized through the regulation of the expression of CDC25a. The results of the present study revealed that let-7c may be a novel target in the diagnosis and treatment of OC.
微小RNA在卵巢癌(OC)的发生发展中发挥作用。本研究调查了let-7c是否能够通过靶向细胞分裂周期25A(CDC25a)来调节OC细胞的增殖。采用逆转录-定量聚合酶链反应检测OC标本中let-7c的表达。将let-7c激动剂转染到OC细胞中,检测OC细胞的增殖和凋亡情况。进行双荧光素酶报告基因检测和蛋白质印迹分析,以分析CDC25a是否为let-7c的靶基因及其相互作用位点。结果显示,与正常卵巢组织相比,OC组织中let-7c表达下调。细胞计数试剂盒-8(CCK8)检测、集落形成检测和流式细胞术表明,let-7c表达增加能够抑制OC细胞的增殖并增加其凋亡。蛋白质印迹显示,let-7c上调能够降低CDC25a的表达,双荧光素酶报告基因检测和回复实验表明,let-7c能够调节CDC25a 3'非翻译区的表达。因此,let-7c抑制OC细胞增殖和促进其凋亡的作用可能是通过调节CDC25a的表达来实现的。本研究结果表明,let-7c可能是OC诊断和治疗的新靶点。