[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) in putative microRNA binding sites (miRSNPs) modulate cancer susceptibility via affecting miRNA binding. Here, we sought to investigate the association between miRSNPs and cervical cancer risk.
We first genotyped 41 miRSNPs of 37 cancer-related genes in 338 patients and 334 controls (Study 1), and replicated the significant associations in 502 patients and 600 controls (Study 2). We tested the effects of miRSNPs on microRNA-mRNA interaction by luciferase reporter assay.
Five SNPs displayed notable association with cervical cancer risk in Study 1. Only IL-16 rs1131445 maintained a significant association with cervical cancer (CT/CC vs. TT, adjusted OR = 1.51, P = 0.001) in Study 2. This association was more evident in the combined data of two studies (adjusted OR = 1.49, P = 0.00007). We also found that miR-135b mimics interacted with IL-16 3'-UTR to reduce gene expression and that the rs1131445 T to C substitution within the putative binding site impaired the interaction of miR-135b with IL-16 3'-UTR. An ELISA indicated that the serum IL-16 of patients with cervical cancer was elevated (vs. controls, P = 0.001) and correlated with the rs1131445 genotype. Patients who carried the rs1131445 C allele had higher serum IL-16 than non-carriers (P<0.001).
These results support our hypothesis that miRSNPs constitute a susceptibility factor for cervical cancers. rs1131445 affects IL-16 expression by interfering with the suppressive function of miR135b and this variant is significantly associated with cervical cancer risk.
PLoS ONE 01/2014; 9(1):e86061. DOI:10.1371/journal.pone.0086061 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pre-eclampsia (PE) is the most serious syndrome of human pregnancy and it is potentially life-threatening for both mother and fetus. The aim of the study was to identify the role of high temperature requirement A1 (HtrA1) in pre-eclampsia.
One hundred consecutive pregnancies complicated by PE and 100 normal controls were included in our study. The changes in serum HtrA1 and fetal growth restriction were recorded. The placentae after delivery was also obtained for laboratory analyses.
High temperature requirement A1 expressed positively in all placenta tissues, but showed higher expression from control, PE with AGA (pre-eclamptic pregnancies with appropriate-for-gestational-age newborns) to PE with fetal growth restriction (FGR) groups. Early-onset PE happened more frequently while in PE with AGA, late-onset PE was more common. Additionally, we found that only during ∼28-32 gestational weeks, sera HtrA1 level of PE with AGA and PE with FGR was increased significantly compared with the control group (p < 0.05). In contrast, there was no significant difference between groups in other gestational ages in the third trimester (p > 0.05).
HtrA1 could potentially affect trophoblast migration and invasion during placentation, resulting in the shallow invasion noted in pre-eclampsia. HtrA1 may play an important role in the etiology and severity of PE and FGR. But the actual mechanism still needs deep research.
Archives of Medical Science 08/2013; 9(4):690-6. DOI:10.5114/aoms.2013.34989 · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective. To investigate the expression and changes of high-temperature requirement A1 (HtrA1) during pregnancy and the use of this value in predicting preeclampsia. Method. Serum samples were collected from pregnant mothers at different gestational weeks, and double-antibody sandwich enzyme-linked immunosorbent assay was employed to describe the changes in HtrA1 in serum during pregnancy. Results. (i) In Xi'an area of China, the incidence of preeclampsia was 4.95%, including 0.85% of early-onset type and 4.10% of late-onset type; (ii) the HtrA1 showed a lognormal distribution during pregnancy in the maternal serum, with the peak at 17-20 weeks of pregnancy; (iii) the HtrA1 levels in preeclampsia mothers peaked at 13-16 weeks of pregnancy, followed by acute decline until 21-24 weeks, then remained stable; (iv) the HtrA1 levels in preeclampsia mothers were higher than the control group in 13-16 weeks and lower than that in 21-24 weeks (p < 0.05); (v) the criteria using lgHtrA1 level at 1.684 during 13-16 weeks of pregnancy could predict hypertension disorders complicating pregnancy (HDCP) with sensitivity of 62.1% and specificity of 53.7%. This could be improved to 85 and 83%, respectively, when combined with body mass index as well as education background of the mother. Conclusion. (i) HtrA1 showed lognormal distribution during pregnancy for all populations; (ii) HtrA1 level peaked at 17-20 weeks in normal group of pregnant mothers, and the increase of HtrA1 level in 13-16 weeks could predict the risk of preeclampsia; (iii) the risk calculation formula for preeclampsia: p (%) = eY/(1 + eY) (Y = -15.87 + 3.706 × lgHtrA1 + 0.134 × mean arterial pressure (MAP) - 1.4 × education level code); e = 2.718.
Hypertension in Pregnancy 05/2012; 31(4):389-97. DOI:10.3109/10641955.2012.667472 · 1.41 Impact Factor