Aberrant expression of BAX, MEG3, and miR-214-3P genes in recurrent pregnancy loss

Abstract

Aims

Recurrent pregnancy loss (RPL), with unknown causes, is one of the most common challenges facing pregnancy. Apoptotic signaling pathways are involved in the normal and abnormal pregnancy process. Despite the evidence pointing toward the aberrant expression of apoptotic and apoptotic-related genes in pregnancy complications, the involvement of these genes in RPL remains to be elucidated. This study aimed to investigate the expression levels of BAX, MEG3, and miR-214-3p (as a microRNA), and their associations in an Iranian population.

Materials and methods

Following the extraction of RNA from blood samples of RPL patients and controls, quantitative expression levels of BAX, MEG3, and miR-214-3p genes were analyzed by real-time RT-PCR.

Results

The findings showed that the expression levels of BAX and miRNA-214-3p were significantly higher in the blood samples of RPL patients than in control samples. In contrast, the expression of MEG3 was significantly down-regulated in women RPL. Furthermore, altered expressions of MEG3 and miRNA-214-3p are associated with their target gene BAX, where the BAX expression is positively and negatively correlated with the expressions of has-miR-214-3P and MEG3, respectively. ROC curve evaluation demonstrated the highest specificity and diagnostic value for miR-214-3p expression in distinguishing RPL samples from the healthy controls.

Conclusions

These data indicated that the aberrant expression of BAX, MEG3, miRNA-214-3p genes in RPL patients could provide new insights into the biological characteristics and related pathways of differentially expressed genes, which could help as potential diagnostic biomarkers and a better understanding of the molecular mechanisms of RPL.

摘要

目的：不明原因的反复妊娠丢失(RPL)是妊娠最常见挑战之一。凋亡信号通路参与正常和异常妊娠过程。尽管有证据表明凋亡和凋亡相关基因在妊娠并发症中异常表达, 但这些基因是否参与RPL仍有待阐明。本研究旨在研究伊朗人群中BAX、MEG3和miR-214-3p(一种microRNA)的表达水平及其与RPL的相关性。

材料和方法:从RPL患者和对照的血液样本中提取RNA后, 用实时RT-PCR分析BAX、MEG3和miR-214-3p基因的定量表达水平。

结果:RPL患者血液中BAX和miRNA-214-3p的表达水平明显高于对照组。相反, 在RPL女性中, MEG3的表达明显下调。此外, MEG3和miRNA214-3p的表达改变与其靶基因BAX相关, 其中BAX表达分别与has-miR-214-3P和MEG3的表达正相关和负相关。ROC曲线评估显示, miR-214-3p表达在区分RPL样本和健康对照中具有最高的特异性和诊断价值。

结论:这些数据表明RPL患者BAX、MEG3、miRNA-214-3p基因的异常表达可为生物学特性和差异表达基因的相关通路提供新的见解, 有助于成为潜在的诊断生物标志物和更好地理解RPL的分子机制。

Keywords:

• Recurrent pregnancy loss
• apoptosis
• MicroRNA
• long non-coding RNA

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Shahid Beheshti University of Medical Sciences [Grant No. 18342].