MicroRNA-34a inhibits human trophoblast cell invasion by targeting MYC.
BACKGROUND
Preeclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. MicroRNA-34a (miR-34a) has been found to be aberrantly expressed in the placentas of preeclamptic patients, yet its role in placental development and in the pathogenesis of preeclampsia remains elusive.


RESULTS
The levels of miR-34a in the placentas of 20 preeclamptic patients and 20 healthy subjects were determined by real time-PCR, and miR-34a was found significantly elevated in the preeclamptic placentas. Further, the function of miR-34a in trophoblast cells was investigated by overexpressing miR-34a in JEG-3 trophoblast cell line. Overexpression of miR-34a in JEG-3 cells inhibited cell proliferation, migration and invasion. In addition, elevated expression of miR-34a reduced the expression of both endogenous and ectopic MYC. Moreover, we identified that MYC mRNA was a direct target of miR-34a in JEG-3 cells by dual luciferase reporter assay, and found that downregulation of MYC expression by miR-34a targeting significantly reduced the invasiveness of JEG-3 cells.


CONCLUSIONS
Our findings provide preliminary evidence for the diverse functions of miR-34a in trophoblast biology, and suggest that miR-34a suppresses trophoblast invasion by directly targeting MYC.
Department of Obstetrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. sunmanni@163.com.
Manni
M
Sun
Department of Obstetrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. Haiying_Chen@outlook.com.
Haiying
H
Chen
Department of Obstetrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. lj_jingliu@126.com.
Jing
J
Liu
Department of Obstetrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. chunxiao.t@outlook.com.
Chunxiao
C
Tong
Department of Obstetrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. mengtao1995@163.com.
Tao
T
Meng
D000328:Adult; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D011247:Pregnancy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
C522425:MIRN34 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc