The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome

J Transl Med. 2018 Aug 17;16(1):231. doi: 10.1186/s12967-018-1600-x.


Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease with huge social-economic impact. It has been suggested that immune dysregulation, nitrooxidative stress, and metabolic impairment might contribute to disease pathogenesis. However, the etiology of ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to play roles in immunological diseases or in stress responses.

Methods: In our study, we examined the expression signature of 10 very long lncRNAs (> 5 kb, CR933609, His-RNA, AK124742, GNAS1-AS, EmX2OS, MIAT, TUG1, NEAT1, MALAT1, NTT) in the peripheral blood mononuclear cells of 44 ME/CFS patients.

Results: LncRNAs NTT, MIAT and EmX2OS levels were found to be significantly elevated in ME/CFS patients as compared with healthy controls. Furthermore, NTT and EmX2OS levels increased with disease severity. Stimulation of human monocytic cell line THP-1 and glioma cell line KALS1 with H2O2 (oxidative stress) and poly (I:C) (double strand RNA, representing viral activation) increased the expression levels of NTT and MIAT.

Conclusions: Our study revealed a ME/CFS-associated very long lncRNA expression signature, which might reflect the regulatory response in ME/CFS patients to oxidative stress, chronic viral infection and hypoxemia. Further investigations need to be done to uncover the functions and potential diagnostic value of these lncRNAs in ME/CFS.

Keywords: Expression signature; Long non-coding RNA; Myalgic encephalomyelitis/chronic fatigue syndrome; Peripheral blood mononuclear cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cell Line, Tumor
  • Fatigue Syndrome, Chronic / genetics*
  • Fatigue Syndrome, Chronic / immunology
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Humans
  • Hypoxia / diagnostic imaging
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Oxidative Stress
  • Principal Component Analysis
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Stress, Physiological
  • Up-Regulation
  • Virus Diseases / physiopathology
  • Young Adult


  • RNA, Long Noncoding