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与子痫前期相关的失调胎盘 RNA 编辑景观。

Landscape of Dysregulated Placental RNA Editing Associated With Preeclampsia.

机构信息

From the Center for Genetics and Developmental Systems Biology, Department of Obstetrics and Gynecology, Nanfang Hospital (Xiaoxue Yang, J.Y., X.L., Q.C., S.J., H.L., Y.G., Z.R., Y.Y., M.Z., Xinping Yang), Southern Medical University, Guangzhou, Guangdong, China.

Key Laboratory of Mental Health of the Ministry of Education (J.Y., Y.G., Xinping Yang), Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Hypertension. 2020 Jun;75(6):1532-1541. doi: 10.1161/HYPERTENSIONAHA.120.14756. Epub 2020 Apr 20.

Abstract

Dysregulated RNA editing is well documented in several diseases, such as cancer and neurodegenerative diseases. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown. Here, we have systematically profiled RNA editome on the placentae, 9 from patients with early-onset severe preeclampsia (EOSPE) and 32 from normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The RNA editing events at 2 microRNA binding sites in 3'-untranslated region of the mRNA were generated, which could inhibit the microRNA-induced mRNA downregulation of in placenta-derived cell line, consistent with the observation in the placentae of preeclampsia patients. These results demonstrate the association of dysregulated placental RNA editing with preeclampsia, and providing a resource for further study on the role of RNA editing in the pathogenesis of this disease.

摘要

RNA 编辑失调在多种疾病中已有充分的记载,如癌症和神经退行性疾病。RNA 编辑是否参与胎盘起源的疾病尚不清楚。在这里,我们系统地对来自 9 名早发性重度子痫前期(EOSPE)患者和 32 名正常受试者的胎盘进行了 RNA 编辑组谱分析,发现 EOSPE 中存在广泛的 RNA 编辑失调。错配编辑的基因集富集了已知与子痫前期相关的基因和 EOSPE 中差异表达的基因。在 mRNA 3'非翻译区的 2 个 microRNA 结合位点产生了 RNA 编辑事件,这可能抑制了胎盘来源细胞系中 mRNA 的 microRNA 诱导下调,与子痫前期患者胎盘的观察结果一致。这些结果表明,胎盘 RNA 编辑失调与子痫前期有关,并为进一步研究 RNA 编辑在该病发病机制中的作用提供了资源。

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