AP2γ 通过作为 ceRNA 下调 lncRNA LINC00511 抑制 miR-29b-3p/Cyr61 轴调控滋养层侵袭。
AP2γ mediated downregulation of lncRNA LINC00511 as a ceRNA suppresses trophoblast invasion by regulating miR-29b-3p/Cyr61 axis.
机构信息
Department of Reproductive Center, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China.
Department of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital Of Hubei University of Arts and Science, Xiangyang 441021, China.
出版信息
Biomed Pharmacother. 2019 Dec;120:109269. doi: 10.1016/j.biopha.2019.109269. Epub 2019 Sep 19.
BACKGROUND
Long noncoding RNA LINC00511 has been identified to be aberrant expression and may as a tumor oncogene in various carcinomas. However, the potential role of LINC00511 in the onset of Preeclampsia (PE) pathogenesis remains unexplored.
METHODS
Placental tissues from patients with PE were collected to detect expression levels of LINC00511 by qRT-PCR. Human HTR-8/SVneo trophoblast cell line was cultured, CCK-8 assay, wound healing assay and transwell assay were performed to determine the regulation of trophoblast biological function by LINC00511. Bioinformatics analysis, chromatin immunoprecipitation (ChIP), luciferases reporter assay were performed to verify the regulatory mechanism of LINC00511.
RESULTS
LINC00511 was aberrantly down-regulated in placental tissues of PE patients. Overexpression of LINC00511 promoted trophoblast cell proliferation, migration and invasion. The transcription factor AP2γ directly binds to the promoter region of LINC00511 to activate transcription. In addition, LINC00511 was enriched in cytoplasm and functioned as a molecular spong for miR-29b-3p, antagonizing its ability to repress Cyr61 protein translation.
CONCLUSION
This study demonstrated that AP2γ mediated downregulation of LINC00511 suppresses trophoblast invasion by regulating miR-29b-3p/ Cyr61 axis.
背景
长链非编码 RNA LINC00511 的表达异常，可能在多种癌症中作为肿瘤癌基因。然而，LINC00511 在子痫前期（PE）发病机制中的潜在作用尚未被探索。
方法
收集 PE 患者的胎盘组织，通过 qRT-PCR 检测 LINC00511 的表达水平。培养人 HTR-8/SVneo 滋养细胞系，通过 CCK-8 测定、划痕愈合试验和 Transwell 试验检测 LINC00511 对滋养细胞生物学功能的调节作用。通过生物信息学分析、染色质免疫沉淀（ChIP）、荧光素酶报告基因试验验证 LINC00511 的调控机制。
结果
PE 患者胎盘组织中 LINC00511 表达异常下调。LINC00511 的过表达促进了滋养细胞的增殖、迁移和侵袭。转录因子 AP2γ 直接结合到 LINC00511 的启动子区域，激活转录。此外，LINC00511 在细胞质中富集，并作为 miR-29b-3p 的分子海绵，拮抗其抑制 Cyr61 蛋白翻译的能力。
结论
本研究表明，AP2γ 介导的 LINC00511 下调通过调节 miR-29b-3p/Cyr61 轴抑制滋养细胞侵袭。
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