The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome, 2018, Chin-An Yang et al

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

  • Chin-An YangView ORCID ID profile,
  • Sandra Bauer,
  • Yu-Chen Ho,
  • Franziska Sotzny,
  • Jan-Gowth Chang† and
  • Carmen Scheibenbogen
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 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.
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https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x
 
This is very interesting.

As ever though, it needs replicating with a different patient group to make sure it is a signature of common pathology and not just an idiosyncratic facet of a localised subtype.

The impression I got was the Charité has a limited patient catchment area, they didn't respond to my emails at any event!
 
Can anybody explain what this is about?

boolybooly said:
The impression I got was the Charité has a limited patient catchment area, they didn't respond to my emails at any event!
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This might be an issue, especially after they ristricted their patient area to Berlin-Brandenburg. But I think the patients in these trials are "older cohorts", so a mix of German patients.

But are all the authors from the Charité, i.e. wouldn't there be patients from another country, too?
 
Well I can try but I am still catching up myself; basically they studied white blood cells and found a type of molecule was expressed more in ME/CFS than in healthy controls.

(NTT, MIAT and EmX2OS.) (nature on MIAT)

So it is indicative of a difference in ME and the nature of the white cell and the molecules concerned implies it is related to an immunological change.

The molecules are three long chain RNAs. We dont know a lot about them, but they are often expressed in conjunction with other pathology for reasons we dont understand yet. e.g. NTT - virus responses, MIAT - myocardial infarction and prostate cancers and EmX2OS - present in normal endometrium but absent in endometrial cancer. As far as I know it does not mean PWME are any more likely to get these other illnesses, it just means the body's response to the conditions creating serious medical conditions in other tissues is as profound at a molecular level as the response to ME in the blood. We just dont know what this means yet but it potentially shows how serious ME is.

These molecules are large and made of RNA which normally encodes genes copied from DNA (as messenger RNA) and short segments of transfer RNA also help decode genes to build proteins in the ribosome. But a molecule is a molecule and sometimes RNA can be used structurally or like an enzyme by biology and evolution which does not mind so much how we classify molecules, as long as it works. In the case of these long chain RNAs we are not sure how they are helping but they do not code for genes and they are far too big to be transfer RNAs... probably... at least not in the conventional sense! So they are a bit of a mystery for now.

That is about as far as I have got with it, one to keep our eyes on but not worth worrying about until more facts are in.
 
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Diwi9 said:
I hope this publication opens the door for more funding of Dr. Scheibenbogen's work.
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Yes! So far government funding in Germany for ME has been zero Euro, but unfortunately it doesn't look like it's going to change anytime soon. The study mentions that it was funded by a grant from the Ministry of Science and Technology Taiwan (and donations from a German charity). Time to step up for Germany.
 
Its not a daft idea IMHO @Jenny TipsforME , I don't think it is possible to say at the moment since the paper analysed cell content not plasma. So we dont know if these particular lncRNAs are released into the plasma in ME.

We do know that other lncRNAs are found in the plasma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631113/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228457/

Even coding RNA tends to be exported out of the nucleus to the endoplasmic reticulum where it makes protein. FYI :)
 
boolybooly said:
As ever though, it needs replicating with a different patient group to make sure it is a signature of common pathology and not just an idiosyncratic facet of a localised subtype.
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It's commonly found in both cancer and neurological disorders, so either way it would not be unique to ME. That's not to be dismissive -- it's an interesting finding and, if it's replicated, could be a way to quantify severity.
 
Merged thread

Could “Junk DNA” Be Causing Chronic Fatigue Syndrome / Myalgic Encephalomyelitis?

http://simmaronresearch.com/2018/11/junk-dna-chronic-fatigue-syndrome-myalgic-encephalomyelitis/

Cort Johnson November 23, 2018

It seems like every time you turn around another part of the genome pops up. It’s amazing how far our knowledge of the human genome has progressed since the Human Genome Project was completed just 15 years ago. Thankfully the small band of researchers involved in chronic fatigue syndrome / myalgic encephalomyelitis (ME/CFS) seem to be keeping up with the latest findings.

Dr. Scheibenbogen seems intent on ploughing new ground. First she re-energized the search for autoantibodies in ME/CFS. Then she examined the effectiveness of a promising treatment called immunoadsorption. With her latest study she and her colleagues at Institute for Medical Immunology, Charité-Universitätsmedizin in Berlin became the first in this disease to examine a peculiar part of our genome called long non-coding RNA’s…
 
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My first thought was we have already checked though its true that DNA testing is only looking at common areas in many cases, unless my knowledge is outdated (possible) full genome is not commonly done or costs a great deal extra
But considering who is doing the research and the fact i can't cognitively read the article i have no opinion at this time because Dr. Scheibenbogen is good at what she does.
 
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