LncRNA FAM83H-AS1 induces nucleus pulposus cell growth via targeting the Notch signaling pathway

J Cell Physiol. 2019 Dec;234(12):22163-22171. doi: 10.1002/jcp.28780. Epub 2019 May 17.

Abstract

Long noncoding RNA (lncRNA) represents a new group of transcripts which act a critical role in various biological and pathological processes. Growing evidence suggested that a new lncRNA, FAM83H-AS1, played important roles in several cancers. However, the underlying mechanisms of FAM83H-AS1-regulating functions in intervertebral disc degeneration (IDD) have yet to be explained. Thus study examined the role of lncRNA FAM83H-AS1 in progression of IDD. First, we proved that expression level of FAM83H-AS1 was expressed in nondegenerated nucleus pulposus (NP) tissues and degenerative NP samples. Moreover, we studied the expression level of FAM83H-AS1 relationship of the clinical disc degeneration grade. Our data suggested that FAM83H-AS1 expression was downregulated in normal NP samples compared with in the degenerated NP samples. FAM83H-AS1 expression was positively correlated with degree of disc degeneration grade. The expression of FAM83H-AS1 was positively correlated with scores of Pfirrmann grade. FAM83H-AS1 expression was increased by IL-1β and TNF-αtreatment in NP cells. Ectopic expression of FAM83H-AS1 induced cell growth and modulated extracellular matrix (ECM) expression in the NP cell. Elevated expression of FAM83H-AS1 promoted Notch1 and Hes1 expression in NP cells. Furthermore, FAM83H-AS1 induced NP cell growth and modulated ECM expression through targeting Notch 1. To conclude, dysregulated expression of FAM83H-AS1 played a crucial role in progression of IDD.

Keywords: FAM83H-AS1; Notch1; lncRNA.

MeSH terms

  • Cell Proliferation / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation
  • Humans
  • Intervertebral Disc Degeneration / genetics
  • Nucleus Pulposus / pathology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Notch / metabolism*
  • Signal Transduction* / drug effects
  • Transcription Factor HES-1 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • RNA, Long Noncoding
  • Receptors, Notch
  • Transcription Factor HES-1
  • Tumor Necrosis Factor-alpha
  • HES1 protein, human