Li Nan, Yang Liang, Sun Yanan, Wu Xiaohua
Department of Gynecology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
Oncol Lett. 2019 Mar;17(3):2631-2638. doi: 10.3892/ol.2019.9923. Epub 2019 Jan 14.
As small non-coding RNA molecules, microRNAs (miRs) function in the regulation of tumorigenesis. Proliferation in ovarian cancer is considered to be associated with miR-16; however, the role of miR-16 in the migration and invasion of ovarian cancer cells remains unclear. The results of the present study demonstrated that miR-16 expression is downregulated in the ovarian cancer SKOV3 and OVCAR3 cell lines compared with that in normal ovarian epithelial cells (OECs). miR-16 overexpression inhibited the proliferation, migration and invasion of SKOV3 and OVCAR3 cells, and decreased the expression of matrix metallopeptidase (MMP)2 and MMP9. Additionally, miR-16 upregulated the expression of cadherin 1, an intercellular adhesion molecule, and downregulated the expression of some mesenchymal markers, including snail family transcriptional repressor 2, snail family transcriptional repressor 1, Vimentin, twist family BHLH transcription factor 1 and cadherin 2 in SKOV3 and OVCAR3 cells. Furthermore, it was indicated that miR-16 overexpression in SKOV3 and OVCAR3 cells resulted in a significant increase in anti-glycogen synthase kinase 3 β expression and a decrease in the expression of Wnt family member 3A, β-catenin, MYC proto-oncogene, BHLH transcription factor and cyclin D1 compared with the NC group. The results of the present study indicated that miR-16 exerts a suppressive effect on cell migration and invasion in ovarian cancer , through inactivation of the Wnt/β-catenin signaling pathway. The data suggest that miR-16 may be a potential therapeutic agent for the treatment and prevention of ovarian cancer.
作为小型非编码RNA分子，微小RNA（miR）在肿瘤发生的调控中发挥作用。卵巢癌的增殖被认为与miR-16有关；然而，miR-16在卵巢癌细胞迁移和侵袭中的作用仍不清楚。本研究结果表明，与正常卵巢上皮细胞（OECs）相比，miR-16在卵巢癌SKOV3和OVCAR3细胞系中的表达下调。miR-16过表达抑制了SKOV3和OVCAR3细胞的增殖、迁移和侵袭，并降低了基质金属蛋白酶（MMP）2和MMP9的表达。此外，miR-16上调了细胞间粘附分子钙粘蛋白1的表达，并下调了SKOV3和OVCAR3细胞中一些间充质标志物的表达，包括蜗牛家族转录抑制因子2、蜗牛家族转录抑制因子1、波形蛋白、扭曲家族BHLH转录因子1和钙粘蛋白2。此外，与NC组相比，SKOV3和OVCAR3细胞中miR-16过表达导致抗糖原合酶激酶3β表达显著增加，Wnt家族成员3A、β-连环蛋白、MYC原癌基因、BHLH转录因子和细胞周期蛋白D1的表达降低。本研究结果表明，miR-16通过Wnt/β-连环蛋白信号通路的失活对卵巢癌细胞的迁移和侵袭发挥抑制作用。数据表明，miR-16可能是治疗和预防卵巢癌的潜在治疗剂。
