Biomarker for abnormal invasion of trophoblast cells and application thereof

A trophoblastic and invasive technology, applied in the field of biomarkers with abnormal trophoblastic invasiveness, can solve problems such as singleness, improve sensitivity and specificity, prevent disease progression, and facilitate detection.

Active Publication Date: 2018-12-07
NANJING MATERNITY & CHILD HEALTH CARE HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, looking at the existing studies, they all start from a single disease (such as: preeclampsia, fetal growth restriction, etc.) to evaluate the correlation between miRNA and trophoblast invasiveness, and lack a comprehensive analysis of such pregnancy-related diseases

Method used

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  • Biomarker for abnormal invasion of trophoblast cells and application thereof
  • Biomarker for abnormal invasion of trophoblast cells and application thereof
  • Biomarker for abnormal invasion of trophoblast cells and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Screening of miRNAs involved in abnormal trophoblast invasiveness

[0025] Two typical disease-related tissues with weakened trophoblastic invasiveness were selected: early spontaneous abortion villi (the maternal progesterone and immune-related indicators were normal, and the prenatal diagnosis center of our hospital ruled out chromosomal abnormalities by karyotype analysis) and preeclampsia placenta, using normal villi and normal placenta as their respective controls, using μParaflo microfluidic chip technology to screen miRNAs with consistent differences between the two groups of diseases.

[0026] The results showed that compared with the control group, there were large differences in miRNAs expression levels in spontaneous abortion villi and preeclampsia placenta tissues; but only 25 miRNAs expression levels were consistent and more than 5 times different between the two groups of diseases, of which 16 expression levels increased, and 9 expression levels...

Embodiment 2

[0027] Example 2: Expression of miR-181b in different diseases related to abnormal trophoblast invasion

[0028] In order to further evaluate the correlation between these three factors and trophoblast invasiveness, we verified them on choriocarcinoma specimens with strong trophoblast invasion.

[0029] Collect 50 cases of spontaneous abortion villi tissues (with insufficient trophoblast invasiveness), and normal villous tissues (with normal trophoblast invasiveness) as a control; at the same time, collect 50 cases of preeclampsia placenta tissues (with insufficient trophoblast invasiveness), and 50 cases of choriocarcinoma tissues Specimens (trophoblasts with excessive invasiveness) and normal placental tissue (trophoblasts with normal invasiveness) were used as controls. Real time PCR or Western Blot technology was used to detect the expression of miR-181b in placenta, chorionic villi and choriocarcinoma tissue samples, and evaluate the relationship with the invasiveness of ...

Embodiment 3

[0034] Example 3: Effect of miR-181b on trophoblast invasiveness

[0035] Bioinformatics analysis found that miR-181b is highly conserved among different species (human, rat, mouse, zebrafish), and the homology is more than 95% (see Table 1), which means that its potential function is important. sex. However, literature review found that there is currently no report on the relationship between miR-181b and trophoblast invasiveness.

[0036] Table 1 Species conservation analysis of miR-181b

[0037]

[0038] In order to obtain more supporting evidence, we used two highly invasive JEG-3 and HTR-8 / Svneo cells as tool cells, and adopted overexpression and silencing strategies to change the expression of miR-181b in cells.

[0039] 1. The effect of miR-181b overexpression on the invasiveness of trophoblast cells:

[0040] The miR-181b lentiviral expression vector was constructed, and the empty lentivirus was used as the control, which was coated into lentiviral particles, and...

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Abstract

The invention relates to a biomarker for abnormal invasion of trophoblast cells and application thereof. It is proved that miR-181b is generally and differentially expressed in pregnancy-related disease tissue with abnormal trophoblast invasion, and S1PR1 is a direct effect target gene of miR-181b; and the discovery of the influence of a miR-181b-S1PR1 pathway on the molecular mechanism of the invasion ability of trophoblast cells provides new clues and potential intervention targets for the prevention and treatment of pregnancy-related diseases caused by abnormal trophoblast invasion.

Description

technical field [0001] The present invention relates to biomarkers of abnormal trophoblast invasiveness and the research on its mechanism, especially the application of miR-181b and its downstream target gene S1PR1 as markers of abnormal trophoblast invasiveness. Background technique [0002] The invasion of trophoblasts is an essential process for embryo implantation and placenta formation. This invasion is surprisingly similar to the invasion and metastasis of tumor cells, but unlike tumor cells, the invasion of trophoblasts is finely regulated and has strict Time and space constraints. The moderate invasiveness of trophoblasts is the key to the establishment, maintenance and timely termination of physiological pregnancy, while the imbalance of invasiveness will cause a variety of pregnancy-related diseases and involve all stages of pregnancy: too weak invasiveness can lead to infertility and miscarriage , premature birth, fetal growth restriction, preeclampsia and other ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12Q1/6883
CPCC12Q1/6883C12Q1/6886C12Q2600/158C12Q2600/178
Inventor 周雪黄骁昊唐冉冉
Owner NANJING MATERNITY & CHILD HEALTH CARE HOSPITAL
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