title: Dissimilar microRNA-21 functions and targets in trophoblastic cell lines of different origin.
abstract: Trophoblast cells express a singular miRNA expression profile which varies during pregnancy and whose alteration may be associated with pregnancy complications. miR-21, a widely known oncomir, is highly expressed in human placenta but its role in regulating trophoblast cells remains unclear. The aim of this study was to investigate miR-21 functions and targets in HTR-8/SVneo immortalized trophoblast and JEG-3 choriocarcinoma cells, which are trophoblast cell models that differ in their cellular origin. Cells were transfected with miR-21-antagomir, -mimic or their respective controls. Following, cell proliferation (BrdU), migration (Transwell and scratch wound-healing assays), invasion (Matrigel assays) and apoptosis (flow cytometry, TUNEL assay and Western blotting) were assessed. Expression of the potential miR-21 targets phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4) were analyzed by Western blotting. Inhibition of miR-21 decreased cell proliferation, migration, and invasion in JEG-3 and HTR-8/SVneo cells and additionally, induced apoptosis in JEG-3 cells. Silencing of miR-21 enhanced PDCD4 expression only in JEG-3 cells, and PTEN expression only in HTR-8/SVneo cells. Inhibition of miR-21 significantly increased phosphorylation of AKT in HTR-8/SVneo cells. In conclusion, miR-21 has cell-specific targets depending upon the origin of trophoblastic cells. Furthermore, miR-21 regulates major cellular processes including cell growth, migration, invasion and apoptosis suggesting that its impairment may lead to placental disorders.
authors: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany; School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
authors: Wittaya
authors: W
authors: Chaiwangyen
authors: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
authors: Stephanie
authors: S
authors: Ospina-Prieto
authors: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
authors: Stella Mary
authors: SM
authors: Photini
authors: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
authors: Ekkehard
authors: E
authors: Schleussner
authors: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany. Electronic address: markert@med.uni-jena.de.
authors: Udo R
authors: UR
authors: Markert
authors: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
authors: Diana M
authors: DM
authors: Morales-Prieto
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Apoptosis; Invasion; MicroRNA; Proliferation; Trophoblast; miR-21