PARP1被miR-519a-3p靶向,促进卵巢癌细胞的迁移、侵袭和管状形成。

Cancer biotherapy & radiopharmaceuticals Pub Date : 2022-11-01 Epub Date: 2021-05-18 DOI:10.1089/cbr.2020.4394
Hua Chang, Xue Zhang, Baixue Li, Xiangkai Meng
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引用次数: 3

摘要

背景:聚adp核糖聚合酶1 (PARP1)已被发现与卵巢癌(OC)有关,但其与microRNA (miR)-519a-3p的相互作用尚不清楚。本研究旨在揭示它们在OC中的作用和相互作用。材料与方法:收集OC患者的临床组织及邻近正常组织,通过Kaplan-Meier曲线分析PARP1高表达或低表达OC患者的生存率。转染后,分别用细胞计数试剂盒-8 (CCK-8)法、划痕法和成管法检测OC细胞活力、迁移和成管。使用TargetScan预测miR-519a-3p的靶基因及其之间的潜在结合位点,并使用双荧光素酶报告基因测定法确认。根据需要采用实时定量聚合酶链反应和Western blot检测miR-519a-3p、PARP1、E-cadherin、N-cadherin、SNAIL、血管内皮生长因子(VEGF)、p53的相对表达。结果:PARP1在OC中表达上调,与OC患者预后不良有关。沉默PARP1降低了PARP1的表达,抑制了OC细胞的活力、迁移、侵袭和管形成,而过表达PARP1则相反。PARP1是miR-519a-3p的靶基因,它通过上调PAR、PARP1、N-cadherin、SNAIL和VEGF的表达,下调E-cadherin和p53的表达,逆转miR-519a-3p对OC细胞迁移、侵袭和成管的影响。结论:PARP1是miR-519a-3p的靶基因,促进OC细胞的迁移、侵袭和成管,为OC患者的治疗提供了可能的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PARP1 Is Targeted by miR-519a-3p and Promotes the Migration, Invasion, and Tube Formation of Ovarian Cancer Cells.
Background: 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. Materials and Methods: 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. Target gene of miR-519a-3p and potential binding sites between them were predicted with TargetScan and confirmed using 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. Results: 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. Conclusion: 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.
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