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PARP1是miR-519a-3p的作用靶点,并促进卵巢癌细胞的迁移、侵袭和血管生成。

PARP1 Is Targeted by miR-519a-3p and Promotes the Migration, Invasion, and Tube Formation of Ovarian Cancer Cells.

作者信息

Chang Hua, Zhang Xue, Li Baixue, Meng Xiangkai

机构信息

Department of Gynecology, The First Hospital of China Medical University, Shenyang, China.

Department of Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

出版信息

Cancer Biother Radiopharm. 2022 Nov;37(9):824-836. doi: 10.1089/cbr.2020.4394. Epub 2021 May 18.

Abstract

Poly ADP-ribose polymerase 1 (PARP1) has been discovered to be implicated in ovarian cancer (OC), but its interaction with microRNA (miR)-519a-3p remained poorly understood. This study aimed to uncover their roles and interactions in OC. Clinical tissue from OC patients and adjacent normal tissue were collected, and the survival rates of OC patients with high or low PARP1 expression were analyzed by Kaplan-Meier curve. After transfection, OC cell viability, migration, and tube formation were detected with cell counting kit-8 (CCK-8) assay, scratch assay, and tube formation assay, respectively. The target gene of miR-519a-3p and potential binding sites between them were predicted with TargetScan and confirmed using a dual-luciferase reporter assay. Relative expressions of miR-519a-3p, PARP1, E-cadherin, N-cadherin, SNAIL, vascular endothelial growth factor (VEGF), and p53 were measured by quantitative real-time polymerase chain reaction and Western blot as needed. PARP1 expression was upregulated in OC, which was related to poor prognosis of OC patients. Silencing PARP1 decreased PARP1 expression and suppressed viability, migration, invasion, and tube formation in OC cells, while overexpressed PARP1 did the opposite. PARP1 was the target gene of miR-519a-3p, and it reversed the effects of miR-519a-3p on the migration, invasion, and tube formation of OC cells by upregulating the expressions of PAR, PARP1, N-cadherin, SNAIL, and VEGF and downregulating those of E-cadherin and p53. PARP1, a target gene of miR-519a-3p, promoted the migration, invasion, and tube formation of OC cells, providing a possible therapeutic target for treatment of OC patients.

摘要

多聚ADP核糖聚合酶1(PARP1)已被发现与卵巢癌(OC)有关,但其与微小RNA(miR)-519a-3p的相互作用仍知之甚少。本研究旨在揭示它们在卵巢癌中的作用及相互作用。收集卵巢癌患者的临床组织和相邻正常组织,采用Kaplan-Meier曲线分析PARP1表达高低的卵巢癌患者的生存率。转染后,分别用细胞计数试剂盒-8(CCK-8)检测、划痕试验和管腔形成试验检测卵巢癌细胞的活力、迁移和管腔形成。用TargetScan预测miR-519a-3p的靶基因及其之间的潜在结合位点,并用双荧光素酶报告基因试验进行验证。根据需要,通过定量实时聚合酶链反应和蛋白质免疫印迹法检测miR-519a-3p、PARP1、E-钙黏蛋白、N-钙黏蛋白、SNAIL、血管内皮生长因子(VEGF)和p53的相对表达。PARP1在卵巢癌中表达上调,这与卵巢癌患者的预后不良有关。沉默PARP1可降低PARP1表达,并抑制卵巢癌细胞的活力、迁移、侵袭和管腔形成,而过表达PARP1则产生相反的效果。PARP1是miR-519a-3p的靶基因,它通过上调PAR、PARP1、N-钙黏蛋白、SNAIL和VEGF的表达以及下调E-钙黏蛋白和p53的表达,逆转了miR-519a-3p对卵巢癌细胞迁移、侵袭和管腔形成的影响。PARP1作为miR-519a-3p的靶基因,促进了卵巢癌细胞的迁移、侵袭和管腔形成,为卵巢癌患者的治疗提供了一个可能的治疗靶点。

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