Roles of noncoding RNAs in preeclampsia

Lu Zhang,Shiting Qin,Ningxia Sun,Shiguo Liu

doi:10.1186/s12958-021-00783-4

Abstract

Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the “junk” of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

Highlights

Preeclampsia (PE) is a pregnancy-related disorder that is associated with the unprecedented onset of hypertension
It accounts for 98% of the human genome, and includes housekeeping ncRNA (transfer RNA, ribosomal RNA, and small nuclear RNA) and regulatory ncRNA (small interfering RNA, microRNA, piwi-interacting RNA, long noncoding RNA, and circular RNA) [8]
Circular RNA (CircRNA) and long noncoding RNAs (lncRNAs) can serve as “sponges” to adjust the availability of miRNAs [14, 15]. ncRNAs can adjust the physiological function of cells by interacting with DNA or proteins [9, 16] The aberrant expression of ncRNAs or their abnormal interactions can lead to the development of various diseases, including PE and cardiovascular disease

Summary

Introduction

Preeclampsia (PE) is a pregnancy-related disorder that is associated with the unprecedented onset of hypertension (systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg). Zhao et al found that when lncRNA HOTAIR is expressed at high levels, it targets miR-106 by binding to EZH2 [139], which in turn inhibits the transcription of the target gene by inducing H3K27 methylation in the promoter region, suppressing the proliferation, migration, and invasion of trophoblasts [190]. The downregulation of lncRNA TUG1 in placental tissues inhibits the proliferation, invasion, and migration of trophoblasts and promotes their apoptosis and it obstructs spiral artery remodeling by reducing the transcriptional regulation of RND3, which is mediated by recruited EZH2 proteins [143]. Zuckerwise et al proposed that the downregulation of H19 inhibits TGF-β signaling transduction by reducing the Par6/Smurf1/RhoA pathway activated by TβR3 [152], Gao et al found that this impairs the migration and invasion of extravillous trophoblasts in vitro by upregulating the expression of miR-let-7 and downregulating the expression of miRNA-675 [150].

Findings

Discussion

Conclusions