Expression Profiles of Exosomal MicroRNAs Derived from Cerebrospinal Fluid in Patients with Congenital Hydrocephalus Determined by MicroRNA Sequencing.

Shiyu Chen,Hao Li,Jicui Zheng,Lili Hao,Anja Hviid Simonsen,Bowen Zhang,Tianrui Jing,Duan Ma,Jing Zhang,Jing Ma,Peixuan Wu

doi:10.1155/2022/5344508

Abstract

Purpose Congenital hydrocephalus is one of the most common birth defects worldwide. Exosomal microRNAs (miRNAs) in body fluids have been implicated in many diseases. However, their involvement in cerebrospinal fluid from congenital hydrocephalus is not well understood. This study is aimed at investigating the role of dysregulated exosomal miRNAs in congenital hydrocephalus. Methods We collected cerebrospinal fluid samples from 15 congenital hydrocephalus patients and 21 control subjects. We used miRNA sequencing to generate exosomal miRNA expression profiles in three pairs of samples. We identified 31 differentially expressed exosomal miRNAs in congenital hydrocephalus and predicted their target mRNAs. Results Three microRNAs (hsa-miR-130b-3p, hsa-miR-501-5p, and hsa-miR-2113) were selected according to their fold changes and the function of their target mRNAs, and only hsa-miR-130b-3p and hsa-miR-501-5p were confirmed their expression levels in all samples. Moreover, upregulated hsa-miR-130b-3p might mediate the downregulation of the phosphatase and tensin homolog gene (PTEN), which has been associated with hydrocephalus, via binding to its 3′-untranslated region by dual-luciferase reporter assay. Conclusion This study implicates that abnormally expressed exosomal miRNAs in cerebrospinal fluid may be involved in the pathomechanism of congenital hydrocephalus.

Highlights

Congenital hydrocephalus (CH) is among the top five birth defects worldwide, with a prevalence of 4.65 in 10,000 births [1]
We verified the differential expression of the above three miRNAs in patients with CH, and we investigated the expression of phosphatase and tensin homolog gene (PTEN), which was associated with hydrocephalus in previous reports [17] via the mechanism of these miRNAs
Extracellular circulating miRNAs exist in most human body fluids, including cerebrospinal fluid, and are highly stable

Summary

Introduction

Congenital hydrocephalus (CH) is among the top five birth defects worldwide, with a prevalence of 4.65 in 10,000 births [1]. As one of the most common congenital central nervous system anomalies, CH results from the accumulation of cerebrospinal fluid in the brain ventricles, leading to severe neurological damage. The main clinical manifestations are ventriculomegaly, increased intracranial pressure, and brain dysfunction, which may lead to dysgnosia, while ventriculomegaly can critically impair the developmental processes affecting various anatomical and functional aspects of brain maturation [2]. Ventriculoperitoneal shunts are common treatments for CH; intracranial pressure may be normal or even low in some patients, including those with other structural brain abnormalities, and surgical shunting may fail to improve the neurological impairment in those patients [2, 3]. It is important to explore the etiology and pathogenesis of CH to improve its prevention and treatment

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