Medical Insurance Management Office, Linyi People's Hospital, Linyi, P.R. China.
Medical Insurance Management Office, Economic and Technological Development Zone People's Hospital of Linyi, Linyi, P.R. China.
J Cell Physiol. 2018 Sep;233(9):7379-7390. doi: 10.1002/jcp.26574. Epub 2018 Mar 25.
Cervical cancer (CC) remains a highly prevalent cancer and mortality globally among women globally. The aim of the present study was to assess the ability of miR-374b to regulate CC cells through JAM-2, whilst exploring whether the underlying mechanism and its relation to the p38/ERK signaling pathway. During the study, microRNA-374b (miR-374b) was observed to have been expressed at a low level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors, siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7 cells. MTT, flow cytometry, scratch test, and transwell assays were applied to determine cell viability, apoptosis, migration, and invasion. The inhibitory role of the p38/ERK signaling pathway was observed in the CC cells treated with miR-374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor exposure was observed to have induced effects on the CC cells in a contrary manner to those induced by that of the miR-374b mimics. The key findings of the study demonstrated that miR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2, highlighting its potential as a therapeutic target for CC.
宫颈癌(CC)仍然是全球女性中一种高发的癌症和死亡率。本研究旨在评估 miR-374b 通过 JAM-2 调节 CC 细胞的能力,同时探索其潜在机制及其与 p38/ERK 信号通路的关系。在研究过程中,观察到 miR-374b 在 CC 组织中的表达水平较低。因此,引入了一系列 miR-374b 模拟物、miR-374b 抑制剂、针对 JAM-2 的 siRNA、SB202190(p38 的抑制剂)和 PD98059(ERK 的抑制剂)来治疗 CC Siha 细胞和正常宫颈 Ect1/E6E7 细胞。MTT、流式细胞术、划痕试验和 Transwell 分析用于测定细胞活力、凋亡、迁移和侵袭。观察到 p38/ERK 信号通路在 miR-374b 模拟物或针对 JAM-2 的 siRNA 处理的 CC 细胞中受到抑制。miR-374b 模拟物暴露被发现降低细胞活力、迁移和侵袭,但诱导凋亡。miR-374b 抑制剂暴露被观察到对 CC 细胞产生与 miR-374b 模拟物相反的作用。研究的主要发现表明,miR-374b 通过阻断 p38/ERK 信号通路的激活以及与 JAM-2 的负性结合,显著抑制细胞增殖、迁移和侵袭,提示其可能成为 CC 的治疗靶点。