title: Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study.
abstract: BACKGROUND
  In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD.
  
  
  METHODS
  An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation.
  
  
  RESULTS
  Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Wan
authors.forename: Fang
authors.initials: F
authors.lastname: Song
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Zhang
authors.forename: Dino
authors.initials: D
authors.lastname: Samartzis
authors.forename: Chi-Jiao
authors.initials: CJ
authors.lastname: Ma
authors.forename: Lu
authors.initials: L
authors.lastname: Che
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: M-Azam
authors.initials: MA
authors.lastname: Ali
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Wang
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D062085:RNA, Long Noncoding