The Second Clinical Medical College, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China.
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710038, P.R. China.
Int J Mol Med. 2019 Nov;44(5):1824-1832. doi: 10.3892/ijmm.2019.4328. Epub 2019 Sep 2.
MicroRNA (miR)‑217 serves a pivotal role in the progression of colorectal cancer, renal cell carcinoma and glioma, however, the role of miR‑217 in cervical cancer (CC) remains unclear. In the present study, the mechanism of miR‑217 in cervical cancer was explored. The mRNA expression of miR‑217 and mitogen‑activated protein kinase 1 (MAPK1) were assessed using reverse transcription‑quantitative polymerase chain reaction analysis. Cell Counting‑Kit 8, wound‑healing and Transwell assays were performed to detect cell viability, migration and invasion, respectively. Apoptosis and cell cycle were determined by flow cytometry. TargetScan 7.2 and dual‑luciferase reporter assays were respectively used to determine miR‑217 target genes and their binding capacities. The protein expression levels of MAPK1, phosphorylated (p)‑extracellular signal‑regulated kinase 1/2 (ERK1/2)/ERK1/2, Bcl‑2, Bax and cleaved caspase‑3 were quantified by western blotting. It was found that miR‑217 was downregulated in patients with CC and in CC cells. The viability, migration and invasion of cells were suppressed by a miR‑217 mimic. It was also found that apoptosis was increased and cell cycle was inhibited by the miR‑217mimic, which was supported by changes in Bcl‑2, Bax and cleaved caspase‑3. MAPK1 was upregulated in patients with CC and was a target gene of miR‑217. MAPK1 reversed the inhibition of miR‑217 on cell viability, migration, invasion and apoptosis. The protein levels of MAPK1 and p‑ERK1/2, which were higher in the mimic MAPK1 group than those in the control or mimic groups, were ameliorated by PD98059. The results of the present study demonstrated that miR‑217 had an anti‑CC effect and may be effectively used in the treatment of CC.
微小 RNA（miR）-217 在结直肠癌、肾细胞癌和神经胶质瘤的进展中发挥着关键作用，然而，miR-217 在宫颈癌（CC）中的作用尚不清楚。在本研究中，探讨了 miR-217 在宫颈癌中的作用机制。采用逆转录-定量聚合酶链反应分析检测 miR-217 和丝裂原活化蛋白激酶 1（MAPK1）的 mRNA 表达。通过细胞计数试剂盒 8 检测、划痕愈合实验和 Transwell 实验分别检测细胞活力、迁移和侵袭。通过流式细胞术检测细胞凋亡和细胞周期。TargetScan 7.2 和双荧光素酶报告基因实验分别用于确定 miR-217 的靶基因及其结合能力。采用 Western blot 法检测 MAPK1、磷酸化（p）-细胞外信号调节激酶 1/2（ERK1/2）/ERK1/2、Bcl-2、Bax 和 cleaved caspase-3 的蛋白表达水平。结果发现，miR-217 在 CC 患者和 CC 细胞中表达下调。miR-217 模拟物可抑制细胞活力、迁移和侵袭。miR-217 模拟物还可增加细胞凋亡，抑制细胞周期，这一结果得到 Bcl-2、Bax 和 cleaved caspase-3 的变化的支持。MAPK1 在 CC 患者中上调，是 miR-217 的靶基因。MAPK1 逆转了 miR-217 对细胞活力、迁移、侵袭和凋亡的抑制作用。在 mimic MAPK1 组中，MAPK1 蛋白和 p-ERK1/2 蛋白的水平高于对照组和 mimic 组，用 PD98059 可改善这一情况。本研究结果表明，miR-217 具有抗 CC 作用，可有效用于 CC 的治疗。
