Identification and Characterization of Serum microRNAs as Biomarkers for Human Disc Degeneration: An RNA Sequencing Analysis.

Shangbin Cui,Xuenong Zou,Songlin Peng,Robert Geoff Richards,Zhen Li,Xizhe Liu,Zhiyu Zhou,Shaoyu Liu,Sibylle Grad,Mauro Alini

doi:10.3390/diagnostics10121063

Abstract

Circulating microRNAs (miRNAs) have been associated with various degenerative diseases, including intervertebral disc (IVD) degeneration. Lumbar disc herniation (LDH) often occurs in young patients, although the underlying mechanisms are poorly understood. The aim of this work was to generate RNA deep sequencing data of peripheral blood samples from patients suffering from LDH, identify circulating miRNAs, and analyze them using bioinformatics applications. Serum was collected from 10 patients with LDH (Disc Degeneration Group); 10 patients without LDH served as the Control Group. RNA sequencing analysis identified 73 differential circulating miRNAs (p < 0.05) between the Disc Degeneration Group and Control Group. Gene ontology enrichment analysis (p < 0.05) showed that these differentially expressed miRNAs were associated with extracellular matrix, damage reactions, inflammatory reactions, and regulation of apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were involved in diverse signaling pathways. The profile of miR-766-3p, miR-6749-3p, and miR-4632-5p serum miRNAs was significantly enriched (p < 0.05) in multiple pathways associated with IVD degeneration. miR-766-3p, miR-6749-3p, and miR-4632-5p signature from serum may serve as a noninvasive diagnostic biomarker for LHD manifestation of IVD degeneration. Furthermore, several dysregulated miRNAs may be involved in the pathogenesis of IVD degeneration. Further study is needed to confirm the functional role of the identified miRNAs.

Highlights

Low back pain (LBP) can cause severe disabilities and is associated with significant personal, social, and economic burden
Twenty patients were enrolled in this study, including 10 patients diagnosed as having Lumbar disc herniation (LDH) (Disc Degeneration Group, DD Group, 53.1 ± 24.2 years old) and 10 patients diagnosed as having other spinal diseases without intervertebral disc (IVD) degeneration (Control Group, 25.1 ± 10.2 years old)
We demonstrate that IVD degeneration with LDH may be modulated by the dysregulation of several miRNAs

Summary

Introduction

Low back pain (LBP) can cause severe disabilities and is associated with significant personal, social, and economic burden. Reports from the Global Burden of Disease Study 2015 showed that 7.3% of the global population (540 million) had activity-limiting LBP in the global point prevalence survey [1]. While the etiology of LBP is multifactorial, it was reported to be associated with IVD degeneration in up to 40% of cases [2]. The etiology of IVD degeneration implies both genetic and environmental factors. Environmental factors such as vibration loading at work, heavy mechanical overload, physical activities, and smoking are weakly accountable for the development and progression of IVD degeneration [4]. Genetic heredity is considered a predominant risk factor for premature IVD degeneration and is believed to be causative in more than 70% of cases [5]

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