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

Abstract

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 H(2)O(2) (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.