Abstract

Background

Congenital heart disease (CHD) is the most universal congenital defect disease. This study explores the interrelationship between miR-23b and GTAT6 in the development of CHD.

Methods

We collected clinical samples and constructed in vitro cell models to evaluate the expression of miR-23b, GATA6, and IGF-1. CHD cell models were constructed by hypoxia in H9C2 cells. The expression levels of GATA6 and IGF-1 in H9C2 cells were determined by western blot and qPCR. MiR-23b was knocked down by transfection miR-23b inhibitor. GATA6 knockdown or overexpression vectors were established by the lentiviral approach and cell transfection, respectively. According to the CCK-8 assay and flow cytometry analysis, the proliferation and apoptosis of H9C2 cells were detected. The binding relationship between GATA6 and miR-23b was detected by luciferase reporter assay.

Results

The expression level of miR-23b was escalated abnormally, while the expression levels of GATA6 and IGF-1 were decreased in the serum of CHD clinical patients and cell models. miR-23b knockdown in H9C2 cells could up-regulate the expression of GATA6, thus improved the proliferation and decreased apoptosis of H9C2 cells. Overexpression of GATA6 could up-regulate IGF-1 to promote proliferation and inhibit apoptosis in H9C2 cells. MiR-23b could target GATA6 and regulated IGF-1, thus affecting cell proliferation and apoptosis.

Conclusion

The expression level of miR-23b was remarkably up-regulated in serum of CHD patients and H9C2 cells in vitro, while the expression of GATA6 and IGF-1 was significantly decreased. MiR-23b could influence the proliferation and apoptosis of cardiomyocytes by targeting the down-regulation of the GATA6/IGF-1 axis.

中文翻译：

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MiR-23b 靶向 GATA6 下调 IGF-1 并促进先天性心脏病的发展

摘要

背景

先天性心脏病（CHD）是最普遍的先天性缺陷疾病。本研究探讨了 miR-23b 和 GTAT6 在 CHD 发展中的相互关系。

方法

我们收集了临床样本并构建了体外细胞模型以评估 miR-23b、GATA6 和 IGF-1 的表达。通过H9C2细胞缺氧构建CHD细胞模型。通过蛋白质印迹和qPCR测定H9C2细胞中GATA6和IGF-1的表达水平。MiR-23b 被转染 miR-23b 抑制剂击倒。GATA6 敲低或过表达载体分别通过慢病毒方法和细胞转染建立。根据CCK-8法和流式细胞仪分析，检测H9C2细胞的增殖和凋亡。GATA6与miR-23b的结合关系通过荧光素酶报告基因检测。

结果

CHD临床患者和细胞模型血清中miR-23b的表达水平异常升高，而GATA6和IGF-1的表达水平降低。H9C2细胞中miR-23b的敲低可以上调GATA6的表达，从而改善H9C2细胞的增殖并减少细胞凋亡。GATA6过表达可上调IGF-1，促进H9C2细胞增殖，抑制细胞凋亡。MiR-23b 可以靶向 GATA6 并调节 IGF-1，从而影响细胞增殖和凋亡。

结论

体外CHD患者血清和H9C2细胞中miR-23b的表达水平显着上调，而GATA6和IGF-1的表达水平显着降低。MiR-23b 可通过靶向下调 GATA6/IGF-1 轴来影响心肌细胞的增殖和凋亡。