microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells

Abstract

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.

Activated mineralocorticoid receptor regulates micro‐RNA‐29b in vascular smooth muscle cells

“…No effect of miR-29b on the size of VSMCs was observed. Although miR-29b-dependent necrosis has not been investigated before, different studies describe proapoptotic effects of miR-29b by targeting antiapoptotic molecules like B-cell lymphoma 2 and myeloid cell leukemia 1 (62)(63)(64). In our experiments, repression of miR-29b led to an enhanced necrosis:apoptosis ratio in vessels.…”

MicroRNAs, immune cells and pregnancy

“…This suggests that miR-29b is involved in the regulation of placental functions including invasion, apoptosis and angiogenesis. 106 Cumulatively, these studies suggest that many different miRNAs present in trophoblast cell populations might contribute to the pathogenesis of pre-eclampsia.…”

“…121 While much of the current literature focuses on miRNA regulation of angiogenesis in cancer, some evidence implicates miRNAs in angiogenesis in reproductive pathologies. In patients with pre-eclampsia, placental angiogenesis is inadequate, and the underdeveloped vasculature is associated with an upregulation of miRNAs (miR-17, -20a, -20b, 127 miR29b 106 and miR-182* 128 ) that target VEGF, and thus inhibit angiogenesis. A recent study has assessed the therapeutic efficacy of miR-126, a pro-angiogenic miRNA, in reversing the inadequate vasculogenesis that occurs in pre-eclampsia.…”

“…105 Another miRNA, miR-29b, that appears to have a similar role to the miR-17-92 cluster, has also been implicated in pre-eclampsia. 106 miR-29b is involved in apoptosis, angiogenesis, and trophoblast invasion. 106 miR-29b regulates the expression of induced myeloid leukemia cell differentiation protein, as well as matrix metalloproteinase-2, and the angiogenic gene, vascular endothelial growth factor (VEGF) A and ITGB1 (integrin beta1) genes.…”

“…106 miR-29b is involved in apoptosis, angiogenesis, and trophoblast invasion. 106 miR-29b regulates the expression of induced myeloid leukemia cell differentiation protein, as well as matrix metalloproteinase-2, and the angiogenic gene, vascular endothelial growth factor (VEGF) A and ITGB1 (integrin beta1) genes. This suggests that miR-29b is involved in the regulation of placental functions including invasion, apoptosis and angiogenesis.…”