microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells.
PE (pre-eclampsia), a pregnancy-specific disorder, is characterized by increased trophoblast cell death and deficient trophoblast invasion and reduced trophoblast-mediated remodelling of spiral arteries. The present study was performed to determine the function of miR-29b (microRNA-29b) in trophoblast cells and its underlying role in the pathogenesis of PE. The prediction of miR-29b target genes was performed using computer-based programs, including Targetscan, Pictar and miRBase. The function of these target genes was analysed further by gene ontology (GO). The effects of miR-29b on apoptosis, and invasion and angiogenesis of trophoblast cell lines (HTR-8/SVneo, BeWo and JAR) were examined by flow cytometry and Matrigel assay respectively. We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin β1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. Taken together, these findings support a novel role for miR-29b in invasion, apoptosis and angiogenesis of trophoblast cells, and miR-29b may become a new potential therapeutic target for PE.
Immunology and Reproductive Biology Lab, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
Pengfei
P
Li
Wei
W
Guo
Leilei
L
Du
Junli
J
Zhao
Yaping
Y
Wang
Liu
L
Liu
Yali
Y
Hu
Yayi
Y
Hou
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D003094:Collagen; D017931:DNA Primers / Q000235:genetics; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000503:physiopathology*; D011247:Pregnancy; D011509:Proteoglycans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004338:Drug Combinations; C108257:ITGB1BP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; C532045:MIRN29a microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011509:Proteoglycans; D019253:Proto-Oncogene Proteins c-bcl-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2