Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR

Tristetraprolin (TTP) regulates the stability of multiple targets that have important biological roles. However, the role of TTP in trophoblasts at the maternal-fetal interface remains poorly understood. We demonstrated that TTP was upregulated in placental trophoblasts from patients with recurrent...

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Main Authors: Fu-Ju Tian (Author), Xiao-Ying He (Author), Jie Wang (Author), Xiao Li (Author), Xiao-Ling Ma (Author), Fan Wu (Author), Jing Zhang (Author), Xiao-Rui Liu (Author), Xiao-Li Qin (Author), Yan Zhang (Author), Wei-Hong Zeng (Author), Yi Lin (Author)
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Published: Elsevier, 2018-09-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Fu-Ju Tian  |e author 
700 1 0 |a Xiao-Ying He  |e author 
700 1 0 |a Jie Wang  |e author 
700 1 0 |a Xiao Li  |e author 
700 1 0 |a Xiao-Ling Ma  |e author 
700 1 0 |a Fan Wu  |e author 
700 1 0 |a Jing Zhang  |e author 
700 1 0 |a Xiao-Rui Liu  |e author 
700 1 0 |a Xiao-Li Qin  |e author 
700 1 0 |a Yan Zhang  |e author 
700 1 0 |a Wei-Hong Zeng  |e author 
700 1 0 |a Yi Lin  |e author 
245 0 0 |a Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR 
260 |b Elsevier,   |c 2018-09-01T00:00:00Z. 
500 |a 2162-2531 
500 |a 10.1016/j.omtn.2018.07.001 
520 |a Tristetraprolin (TTP) regulates the stability of multiple targets that have important biological roles. However, the role of TTP in trophoblasts at the maternal-fetal interface remains poorly understood. We demonstrated that TTP was upregulated in placental trophoblasts from patients with recurrent miscarriages (RMs). Immunofluorescence and immunoblotting analyses indicated that TTP was redistributed from the nucleus to the cytoplasm in trophoblasts from patients with RMs. Trophoblast invasion and proliferation was repressed by TTP overexpression and was enhanced by TTP knockdown. Interestingly, TTP knockdown promoted trophoblast invasion in an ex vivo explant culture model. Furthermore, TTP overexpression in trophoblasts significantly inhibited the expression of the long non-coding RNA (lncRNA) HOTAIR. TTP was found to regulate HOTAIR expression by a posttranscriptional mechanism. To RNA immunoprecipitation (RIP) and RNA-protein, pull-down identified TTP as a specific binding partner that decreased the half-life of HOTAIR and lowered steady-state HOTAIR expression levels, indicating a novel posttranscriptional regulatory mechanism. Our findings identify a novel function for TTP in lncRNA regulation and provide important insights into the regulation of lncRNA expression. This study reveals a new pathway governing the regulation of TTP/HOTAIR in trophoblast cell invasion during early pregnancy. Keywords: TTP, HOTAIR, trophoblast invasion, RNA destabilizing, recurrent miscarriage 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Molecular Therapy: Nucleic Acids, Vol 12, Iss , Pp 600-609 (2018) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2162253118301410 
787 0 |n https://doaj.org/toc/2162-2531 
856 4 1 |u https://doaj.org/article/ce097d189b9c47d08d0ddbad3d4a7c46  |z Connect to this object online.