MiR-222-5p promotes the growth and migration of trophoblasts by targeting AHNAK.

OBJECTIVE: The purpose of this study was to detect microRNA-222-5p (miR-222-5p) levels in placental tissues of preeclampsia (PE) pregnancies, and to explore the role of miR-222-5p in the proliferative and migratory potentials of trophoblast cell line HTR-8/SVneo. PATIENTS AND METHODS: Expression levels of miR-222-5p and AHNAK in placental tissues of PE pregnancies (n=24) and healthy pregnancies (n=24) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Potential influences of miR-222-5p and AHNAK on proliferative, migratory and apoptotic potentials in HTR-8/SVneo cells were examined. At last, Luciferase assay was conducted to illustrate the interaction between miR-222-5p and AHNAK in trophoblasts. RESULTS: It was found that miR-222-5p was downregulated in placental tissues of PE pregnancies. Overexpression of miR-222-5p stimulated proliferative and migratory potentials, and inhibited apoptosis in HTR-8/SVneo cells. Moreover, AHNAK was the target gene binding to miR-222-5p, and overexpression of AHNAK inhibited proliferative and migratory potentials and promoted apoptosis in HTR-8/SVneo cells. CONCLUSIONS: MiR-222-5p stimulates proliferative and migratory potentials and inhibits apoptosis in HTR-8/SVneo cells by negatively regulating AHNAK.

Correlations of CYP11B2 gene polymorphisms with eclampsia.

OBJECTIVE: The aim of this study was to explore the relationship between CYP11B2 gene polymorphisms and eclampsia. PATIENTS AND METHODS: A total of 400 pregnant women treated in our hospital were enrolled in this study, including 200 normal pregnant women (pregnancy group) and 200 pregnant women with eclampsia (eclampsia group). Peripheral blood was collected from subjects of the two groups. Subsequently, genomic deoxyribonucleic acids (DNAs) were extracted and amplified via polymerase chain reaction (PCR) for detection of CYP11B2 rs4543, rs3802228 and rs104894072 polymorphisms. The expression level of CYP11B2 gene was measured as well. Additionally, the correlations of CYP11B2 gene polymorphisms with blood pressure and coagulation and renal function indexes were analyzed. RESULTS: The distribution of alleles of rs4543 locus in CYP11B2 gene was significantly different between eclampsia group and pregnancy group (p=0.027). The frequency of the allele C was significantly lower in eclampsia group than that of pregnancy group (p<0.05). There was a statistically significant difference in the genotype distribution of CYP11B2 rs3802228 (p=0.000) and rs104894072 (p=0.000) between eclampsia group and pregnancy group (p<0.05). Meanwhile, the frequency of AA genotype of rs3802228 and TG genotype of rs104894072 was remarkably higher in eclampsia group than that in pregnancy group (p<0.05). The distribution of the locus rs104894072 (p=0.044) in dominant model and rs3802228 (p=0.002) in recessive model in eclampsia group was different from that in pregnancy group (p<0.05). Eclampsia group showed remarkably elevated frequency of TT + TG of the locus rs104894072 in dominant model and lowered frequency of AG + GG of the locus rs3802228 in recessive model (p<0.05). Similarly, a significant difference was observed in the distribution of the haplotypes CGG (p=0.001) and TGT (p=0.048) in CYP11B2 gene between eclampsia group and pregnancy group (p<0.05). The linkage disequilibrium of the loci rs3802228 and rs104894072 was relatively high (D'=0.382). The polymorphism of the locus rs104894072 in CYP11B2 gene had an evident relation to CYP11B2 gene expression (p<0.05). Meanwhile, the expression of CYP11B2 gene was markedly higher in patients with GG genotype in eclampsia group (p<0.05). The polymorphism of CYP11B2 rs4543 was notably associated with PT level of patients in eclampsia group (p=0.000). Conversely, rs3802228 polymorphism was correlated with 24 h urine protein level (p=0.000). Besides, the proportion of patients with CGG haplotype was significantly larger among patients with systolic blood pressure of 140-160 mmHg (p<0.05). In addition, the proportion of patients with TGT haplotype was evidently greater among patients with systolic blood pressure >180 mmHg in eclampsia group (p<0.05). CONCLUSIONS: CYP11B2 gene polymorphisms are significantly correlated with the development and progression of eclampsia.

MiR-134 inhibits infiltration of trophoblast cells in placenta of patients with preeclampsia by decreasing ITGB1 expression.

OBJECTIVE: Preeclampsia (PE) is an idiopathic disorder of pregnancy. The specific regulatory mechanisms of microRNAs (miRs) in the placenta of PE patients have not yet been completely revealed. This study mainly explored the mechanism of miR-134 in preeclampsia. PATIENTS AND METHODS: Real-time PCR and Western blot were used to detect the expression of miR-134 and ITGB1 in the placenta of patients with preeclampsia and normal pregnant women. Dual luciferase reporter assay was performed to detect luciferase activity in miR-134 and NC groups, respectively. Cell proliferation ability after transfection was evaluated by MTS colorimetric assay, and the effect of miR-134 on the infiltration of trophoblast cells was explored by cell invasion experiment. In addition, co-transfection of miR-134 and ITGB1 expression plasmids was carried out, and then changes in the cell invasiveness were also detected by cell invasion experiment. RESULTS: Compared with placenta of normal pregnant women, miR-134 was significantly up-regulated in the placenta of patients with preeclampsia and negatively correlated with the expression of ITGB1. MiR-134 suppressed the infiltration of trophoblast cells by targeting ITGB1. When ITGB1 was overexpressed, the suppression of invasiveness of trophoblast cells by miR-134 was almost abolished. Meanwhile, we found that miR-134 inhibitor could promote the invasiveness of trophoblast cells. In addition, tumor necrosis factor-α (TNF-α) was found to enhance miR-134 expression as well as inhibit ITGB1 expression. CONCLUSIONS: MiR-134 inhibited the infiltration of trophoblast cells in preeclampsia by down-regulating ITGB1 expression.