MicroRNA-128a-induced apoptosis in HTR-8/SVneo trophoblast cells contributes to pre-eclampsia.
BACKGROUND
Pre-eclampsia (PE) can endanger the survival of the mother and fetus. Currently, the pathogenesis of PE is not completely understood and no fundamental therapeutics are available. The present study was performed to determine the function of miR-128a in HTR-8/SVneo trophoblast cells and to ascertain its underlying role in the pathogenesis of PE.


METHODS
We investigated the function of miR-128a in HTR-8/SVneo cells by overexpressing. We analyzed the apoptosis of HTR-8/SVneo cells by performing apoptosis assays and measured the loss of mitochondrial membrane potential (Δym), the generation of reactive oxygen species (ROS) and caspase activity. In addition, miR-128a target genes were predicted.


RESULTS
Using computer-based programs, we identified Bax as a direct target of miR-128a. In the apoptosis assays of HTR-8/SVneo cells, miR-128a decreased the Δψm, depleted ATP levels and increased ROS generation, cytochrome c release as well as caspase activation. Further studies showed that miR-128a induced the apoptosis of HTR-8/SVneo cells by down-regulating Bax through the mitochondrial apoptosis pathway.


CONCLUSIONS
miR-128a is an up-regulated miRNA in patient with PE. Our study demonstrated that the miR-128a-induced apoptosis of HTR-8/SVneo cells may contribute to PE and miR-128a may be a novel potential therapeutic target for PE.
Department of Obstetrics and Gynecology, Yangzhou Maternal and Child Health Hospital, Affiliated with Yangzhou Medical University, China.
Gui-Chun
GC
Ding
State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternal and Child Health Hospital, Affiliated with Nanjing Medical University, China.
Min
M
Chen
Department of Obstetrics and Gynecology, Yangzhou Maternal and Child Health Hospital, Affiliated with Yangzhou Medical University, China.
Yi-Xiong
YX
Wang
State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternal and Child Health Hospital, Affiliated with Nanjing Medical University, China.
Can
C
Rui
Department of Obstetrics and Gynecology, Yangzhou Maternal and Child Health Hospital, Affiliated with Yangzhou Medical University, China.
Wen
W
Xu
State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternal and Child Health Hospital, Affiliated with Nanjing Medical University, China. Electronic address: dinghj_njfy@163.com.
Hong-Juan
HJ
Ding
State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternal and Child Health Hospital, Affiliated with Nanjing Medical University, China. Electronic address: jesse_1982@163.com.
Zhong-Hua
ZH
Shi
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D004272:DNA, Mitochondrial; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D020169:Caspases
Apoptosis; Bax; Mitochondria; Pre-eclampsia; miR-128a; microRNA