Department of Gynecology and Obstetrics, Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, China.
Yonsei Med J. 2021 Jun;62(6):535-544. doi: 10.3349/ymj.2021.62.6.535.
Long non-coding RNAs (lncRNAs) are essential regulators in the development of ovarian cancer (OC). Nonetheless, the function of lncRNA DNM3 opposite strand/antisense RNA (DNM3OS) in OC remains unclear. This work aimed to investigate the biological roles and underlying mechanisms of DNM3OS in OC.
Quantitative real-time polymerase chain reaction was conducted to examine DNM3OS, microRNA (miR)-193a-3p, and mitogen-activated protein kinase 3 (MAP3K3) mRNA expression in OC tissues and cell lines. Kaplan-Meier survival analysis was employed to analyze the relationship between DNM3OS expression and the prognosis of OC patients. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell experiments were conducted to monitor cell proliferation, migration, and invasion, respectively. Western blot was applied to examine epithelial-mesenchymal transition associated protein (E-cadherin and N-cadherin) expression. Luciferase reporter gene and RNA immunoprecipitation experiments were performed to confirm the relationships among DNM3OS, miR-193a-3p, and MAP3K3. Pearson's correlation analysis was adopted to analyze the correlations among DNM3OS, miR-193a-3p, and MAP3K3 mRNA.
DNM3OS expression was remarkably increased in OC tissues and cell lines, which was associated with the unfavorable prognosis of the patients. DNM3OS overexpression enhanced OC cell proliferation, migration, and invasion; suppressed E-cadherin protein expression; and facilitated N-cadherin protein expression, while the transfection of miR-193a-3p mimics had the opposite effects. DNM3OS directly interacted with miR-193a-3p, and miR-193a-3p targeted MAP3K3 by directly binding to 3'UTR. DNM3OS could up-regulate the expression of MAP3K3 via repressing miR-193a-3p expression.
DNM3OS, as an oncogenic lncRNA, increases the malignancy of OC cells via regulation of an miR-193a-3p/MAP3K3 axis.
长链非编码 RNA（lncRNA）是卵巢癌（OC）发展的重要调控因子。然而，lncRNA DNM3 反义链/反义 RNA（DNM3OS）在 OC 中的功能尚不清楚。本研究旨在探讨 DNM3OS 在 OC 中的生物学作用和潜在机制。
采用实时定量聚合酶链反应检测 OC 组织和细胞系中 DNM3OS、微小 RNA（miR）-193a-3p 和丝裂原活化蛋白激酶 3（MAP3K3）mRNA 的表达。Kaplan-Meier 生存分析用于分析 DNM3OS 表达与 OC 患者预后的关系。细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷和 Transwell 实验分别用于监测细胞增殖、迁移和侵袭。Western blot 用于检测上皮-间充质转化相关蛋白（E-钙黏蛋白和 N-钙黏蛋白）的表达。荧光素酶报告基因和 RNA 免疫沉淀实验用于证实 DNM3OS、miR-193a-3p 和 MAP3K3 之间的关系。Pearson 相关分析用于分析 DNM3OS、miR-193a-3p 和 MAP3K3 mRNA 之间的相关性。
DNM3OS 在 OC 组织和细胞系中表达显著增加，与患者的不良预后相关。DNM3OS 过表达增强 OC 细胞的增殖、迁移和侵袭；抑制 E-钙黏蛋白蛋白表达；促进 N-钙黏蛋白蛋白表达，而 miR-193a-3p 模拟物的转染则产生相反的效果。DNM3OS 直接与 miR-193a-3p 相互作用，miR-193a-3p 通过直接结合 3'UTR 靶向 MAP3K3。DNM3OS 通过抑制 miR-193a-3p 的表达上调 MAP3K3 的表达。
DNM3OS 作为一种癌基因 lncRNA，通过调节 miR-193a-3p/MAP3K3 轴增加 OC 细胞的恶性程度。
