Genome-Wide Identification of Long Noncoding RNAs in Human Intervertebral Disc Degeneration by RNA Sequencing.

Bo Zhao,Haopeng Li,Minjuan Lu,Xijing He,Dong Wang

doi:10.1155/2016/3684875

Bo Zhao, Haopeng Li + Show 3 more

Open Access

https://doi.org/10.1155/2016/3684875

Copy DOI

Abstract

Long noncoding RNAs (lncRNAs) are emerging as crucial players in a myriad of biological processes. However, the precise mechanism and functions of most lncRNAs are poorly characterized. In this study, we presented genome-wide identification of lncRNAs in the patients with intervertebral disc degeneration (IDD) and spinal cord injury (control) using RNA sequencing (RNA-seq). A total of 124.6 million raw reads were yielded using Hiseq 2500 platform and approximately 88% clean reads could be aligned to human reference genome in both IDD and control groups. RNA-seq profiling indicated that 1,854 lncRNAs were differentially expressed (log2 fold change ≥ 1 or ≤−1, p < 0.05), in which 1,530 could potentially target 6,386 genes via cis-regulatory effects. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for these target genes suggested that lncRNAs were involved in diverse pathways, such as lysosome, focal adhesion, and MAPK signaling. In addition, a competing endogenous RNA (ceRNA) network was constructed for analyzing the function of lncRNAs. Further, quantitative real time PCR (qRT-PCR) was used to confirm the differentially expressed lncRNAs and ceRNA network. In conclusion, our results present the first global identification of lncRNAs in IDD and may provide candidate diagnostic biomarkers for IDD treatment.

Highlights

Intervertebral disc degeneration (IDD) is implicated as the major contributor of low back pain, which inflicts global burden with severe health care [1, 2]
To classify the differentially expressed Long noncoding RNAs (lncRNAs) according to their position with protein-coding genes, we identified that vast majority were sense lncRNA (1302), followed by intergenic lncRNA (252), intronic lncRNA (134), small RNA (sRNA) host lncRNA (64), antisense lncRNA (59), and bidirectional lncRNA (35), as well as eight lncRNAs that could not be classified well (Supplementary Table 3)
We present the comprehensive identification and analysis of IDD specific lncRNAs using RNA sequencing (RNA-seq)

Summary

Introduction

Intervertebral disc degeneration (IDD) is implicated as the major contributor of low back pain, which inflicts global burden with severe health care [1, 2]. Small ncRNAs include many types, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and PIWIinteracting RNAs (piRNA), which have regulatory roles during diverse biological events [8]. Among these small ncRNAs, miRNAs are studied extensively in IDD, and we compared the expression of miRNAs between IDD and spinal cord injury specimens in previous study [9]. LncRNAs are initially considered as nonfunctional byproducts of RNA polymerase II transcripts and have been paid much attention recently because they may act as important cis- or trans-regulators in a wide variety of biological functions, such as gene expression, genome imprinting, chromatin modification, and epigenetic regulation as well [10,11,12]. LncRNAs have been applied in the treatment of disease, such as cancer, neurodegenerative, and psychiatric diseases [13, 14]

Methods

Results

Conclusion