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Paper: long non-coding RNA in ME/CFS

Discussion in 'Latest ME/CFS Research' started by boolybooly, Aug 19, 2018.

  1. boolybooly

    boolybooly Senior Member

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    Dr Fluks kindly posted this to an email group, I thought I better pass it on. Shows a signature in long non coding / functional RNA expression of sequences previously associated with immune processes.

    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x

     
    Murph, Wolfcub, Wishful and 2 others like this.
  2. Belbyr

    Belbyr

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    If anyone can break this down into something easily understandable, I'm all ears...
     
  3. boolybooly

    boolybooly Senior Member

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    OK I can repost the following, which is my take on it posted elsewhere.

     
    Mel9 likes this.
  4. Murph

    Murph :)

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    Full text is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098652/

    Seems long, non-coding RNA (LncRNA) can turn genes on and off. It is a relatively new discovery in disease.They're not too sure what role it plays in disease, but they keep finding it on the scene in a suspicious way. They're mostly just cataloguing the fact that something is going on with these, certainly not finding a cure right now.

    "Emerging roles of very large (> 5 kb) lncRNAs in immune regulation and disease processes are being discovered."

    The role of LncRNA is still a bit ?

    LncRNAs are key regulators of chromatin state, which show great capacity to interact with more than one protein in different context, and fine-tune the cellular response [8]. It has been reported that lncRNAs play essential roles in complex diseases, such as cancer and autoimmune diseases [911]. Although more and more lncRNAs are being discovered, most of their functions and mechanisms of actions are still unknown, especially for the very large lncRNAs that have sizes of more than 5000 nucleotides. We had particular interests in ten very large lncRNAs (> 5 kb), which have been either reported to be involved in immune regulation, or are located close to genes regulating stress response, metabolic and neurologic processes, thus potentially playing a role in ME/CFS.


    Here's a graphic showing healthy controls and patients with high and low functioning (as measured by Bell scores) Only three of the RNAs are significantly upregulated in mecfs: NTT, MIAT, EM2XOS.


    Screen Shot 2018-08-26 at 7.58.29 AM.png

    Some details on the ten lncRNAs. I underlined the ones that showed significant difference in MECFS.

    The ten lncRNAs are NTT (17 kb), NEAT1 (23 kb), MALAT1 (7.5 kb), TUG1 (7.1 kb), MIAT (9.9 kb), His-1 RNA (8.4 kb), GNAS1-AS (8.9 kb), EMX2OS (7.3 kb), CR933609 (8.8 kb) and AK124742 (6 kb). NTT was first described in activated T cells, while NEAT1 has been reported to be involved in human lupus and in immune response to viral infections [1113]. MALAT1 has been found to regulate LPS-induced inflammatory response, and TUG1 is involved in the regulation of cold-induced oxidative stress and inflammation [1416]. As for MIAT, it is known to play roles in a variety of disease processes, including myocardial infarction, microvascular dysfunction, schizophrenia, and neurogenic commitment [17, 18].

    His-1 RNA has been implicated in leukemogenesis, and GNAS1-AS is an imprinted anti-sense transcript at the locus of GNAS1, encoding neuroendocrine secretory protein [19, 20]. According to the lncrnadb database, EMX2OS is an opposite strand transcript of EMX2 gene, and possibly regulates EMX2 [21]. Both EMX2OS and EMX2 RNAs have been detected in the central nervous system (CNS) tissues [22]. For CR933609, we have previously identified its role in protecting INO80D from downregulation by miRNA-5096 [23]. Since INO80D is a main component of the chromatin re-modeler INO80 complex which regulates cell glycolytic and respiratory capacities, CR933609 could be involved in maintaining metabolic stability [24]. Finally, AK124742 has been reported to be an antisense RNA to the gene PSMD6, which encodes components of proteasome, involving antigen presentation by MHC class I and DNA damage repair [25, 26].

    They mention these RNAs as a possible biomarker with a decent but not spectacular ability to discriminate cases from controls, pending further studies:


    Using expression of any two of these three lncRNAs (NTT, MIAT and EMX2OS) in discriminating ME/CFS from healthy had an AUC of 0.82 on ROC curve, suggesting a potential diagnostic value of these lncRNAs for ME/CFS....

    ... However, we do not know yet whether this lncRNA profile found in our study is specific for ME/CFS or can be found in other diseases involving immune dysregulation or oxidative stress, such as autoimmune diseases and cancer. It has been reported that MIAT levels could be upregulated in high glucose conditions and in lung cancer, and NTT expressions might be found in processes involving T cell activation [12, 17, 29]. Further comparing the PBMC expression signature of NTT, MIAT, and EMX2OS in ME/CFS with patients suffering from chronic fatigue due to autoimmune diseases or cancer is important to assess the lncRNA test specificity in diagnosing ME/CFS.

    So this is mostly a discovery of a molecular feature of this disease, that affirms its physical reality and for now does not suggest any treatment. It is more just to bank the discovery away in case oncology researchers hit upon some meaning or use of LncRNA.
     

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    sb4 likes this.

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