Li Ziwei, Zhou Xinyi, Gao Wenyan, Sun Manni, Chen Haiying, Meng Tao
Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, China.
China Medical University, Shenyang, China.
J Cell Mol Med. 2022 Mar;26(6):1826-1841. doi: 10.1111/jcmm.16454. Epub 2021 Mar 18.
Pre-eclampsia (PE) is a worldwide pregnancy-related disorder. It is mainly characterized by defect migration and invasion of trophoblast cells. Recently, circular RNAs (circRNAs) have been believed to play a vital role in PE. The expression patterns and the biological functions of circRNAs in PE remain elusive. Here, we performed a circRNA microarray to identify putative PE-related circRNAs. Bioinformatics analyses were used to screen the circRNAs which have potential relationships with pre-eclampsia, and we identified a novel circRNA (circVRK1) that was up-regulated in PE placenta tissues. By using HTR-8/SVneo cells, circVRK1 knockdown significantly enhanced cell migration and invasion abilities, as well as epithelial-mesenchymal transition (EMT). Mechanistically, we found that circVRK1 and PTEN could function as the ceRNAs to miR-221-3p. Overexpression of miR-221-3p promoted cell migration, invasion and EMT via regulating PTEN. The cotransfection of miR-221-3p inhibitor or PTEN reversed the effect from circVRK1 knockdown. Moreover, the circVRK1/miR-221-3p/PTEN axis greatly regulated Akt phosphorylation. In general, circVRK1 suppresses trophoblast cell migration, invasion and EMT, by acting as a ceRNA to miR-221-3p to regulate PTEN, and further inhibit PI3K/Akt activation. The purpose of this paper is to open wide insights to investigate the onset of PE and provide new potential therapeutic targets in PE.
子痫前期（PE）是一种全球性的妊娠相关疾病。其主要特征是滋养层细胞的迁移和侵袭缺陷。最近，环状RNA（circRNAs）被认为在PE中起重要作用。circRNAs在PE中的表达模式和生物学功能仍不清楚。在此，我们进行了circRNA微阵列分析以鉴定假定的与PE相关的circRNAs。利用生物信息学分析筛选与子痫前期有潜在关系的circRNAs，我们鉴定出一种新的circRNA（circVRK1），其在PE胎盘组织中上调。通过使用HTR-8/SVneo细胞，circVRK1敲低显著增强了细胞迁移和侵袭能力以及上皮-间质转化（EMT）。机制上，我们发现circVRK1和PTEN可作为miR-221-3p的竞争性内源RNA（ceRNAs）。miR-221-3p的过表达通过调节PTEN促进细胞迁移、侵袭和EMT。miR-221-3p抑制剂或PTEN的共转染逆转了circVRK1敲低的作用。此外，circVRK1/miR-221-3p/PTEN轴极大地调节Akt磷酸化。总体而言，circVRK1通过作为miR-221-3p的ceRNA来调节PTEN，进而抑制PI3K/Akt激活，从而抑制滋养层细胞的迁移、侵袭和EMT。本文旨在为研究PE的发病机制提供广泛的见解，并为PE提供新的潜在治疗靶点。
