Pseudogene fms-related tyrosine kinase 1 pseudogene 1 (FLT1P1) cooperates with RNA binding protein dyskeratosis congenita 1 (DKC1) to restrain trophoblast cell proliferation and angiogenesis by targeting fms-related tyrosine kinase 1 (FLT1) in preeclampsia

被引:5
作者
Chi, Zhenjing [1 ]
Sun, Yanlan [1 ]
Yu, Zhou [1 ]
Zhou, Fenmei [1 ]
Wang, Hairong [1 ]
Zhang, Muling [1 ]
机构
[1] Nanjing Med Univ, Dept Obstet, Affiliated Huaian 1 Peoples Hosp, 1 Huanghe West Rd, Huaian 223300, Jiangsu, Peoples R China
关键词
DKC1; FLT1; preeclampsia; COMPETING ENDOGENOUS RNA; APOPTOSIS; EXPRESSION; MIGRATION; DYSFUNCTION; INVASION; GENE;
D O I
10.1080/21655979.2021.1988366
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In preeclampsia (PE), preexistent maternal endothelial dysfunction leads to impaired placentation and vascular maladaptation. Long noncoding RNAs (lncRNAs) have been shown to participate in the placentation process. LncRNA fms-related tyrosine kinase 1 pseudogene 1 (FLT1P1) was previously reported to be upregulated in PE. In this study, we verified the effect of FLT1P1 and its cognate gene FLT1 on trophoblast cell proliferation and angiogenesis by using Cell Counting Kit-8 (CCK-8) assay, tube formation assay, and western blot analysis. Their binding to RNA binding protein dyskeratosis congenita 1 (DKC1) was validated by conducting RNA immunoprecipitation (RIP) and RNA pulldown assays. In this study, knockdown of FLT1P1 or FLT1 was found to promote cell proliferation and angiogenesis in trophoblasts. In addition, FLT1P1 recruited DKC1 to stabilize FLT1. Importantly, silencing FLT1P1 or DKC1 decreased the stability of FLT1. Rescue assays revealed that FLT1 overexpression reversed the effect of silenced FLT1P1. Overall, FLT1P1 cooperates with DKC1 to restrain trophoblast cell proliferation and angiogenesis by targeting FLT1.
引用
收藏
页码:8885 / 8897
页数:12
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