Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
Division of General Pediatrics, Children's Hospital of China Medical University, Taichung, Taiwan.
J Transl Med. 2018 Aug 17;16(1):231. doi: 10.1186/s12967-018-1600-x.
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.
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.
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 HO (oxidative stress) and poly (I:C) (double strand RNA, representing viral activation) increased the expression levels of NTT and MIAT.
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.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种慢性衰弱性疾病，具有巨大的社会经济影响。有人认为免疫失调、硝基氧化应激和代谢损伤可能有助于疾病的发病机制。然而，ME/CFS 的病因在很大程度上仍不清楚，也缺乏诊断/预后疾病标志物。已经有报道称，几种长非编码 RNA（lncRNA，>200bp）在免疫性疾病或应激反应中发挥作用。
在我们的研究中，我们检测了 44 名 ME/CFS 患者外周血单个核细胞中 10 种非常长的 lncRNA（>5kb，CR933609、His-RNA、AK124742、GNAS1-AS、EmX2OS、MIAT、TUG1、NEAT1、MALAT1、NTT）的表达谱。
与健康对照组相比，ME/CFS 患者的 lncRNA NTT、MIAT 和 EmX2OS 水平明显升高。此外，NTT 和 EmX2OS 水平随着疾病严重程度的增加而升高。用 HO（氧化应激）和 poly（I:C）（双链 RNA，代表病毒激活）刺激人单核细胞系 THP-1 和神经胶质瘤细胞系 KALS1，可增加 NTT 和 MIAT 的表达水平。
我们的研究揭示了一个与 ME/CFS 相关的非常长的 lncRNA 表达谱，它可能反映了 ME/CFS 患者对氧化应激、慢性病毒感染和低氧血症的调节反应。需要进一步的研究来揭示这些 lncRNAs 在 ME/CFS 中的功能和潜在的诊断价值。
