Unravelling .. (ME/CFS): Gender‐specific changes in the microRNA expression profiling in ME/CFS, 2020, Cheema, Klimas et al

Andy

Retired committee member
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state.

Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS. The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post‐exertional malaise in ME/CFS.

We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects' metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements. The identification of gender‐based miRNAs importantly provides new insights into gender‐specific ME/CFS susceptibility and demands exploration of sex‐suited ME/CFS therapeutics.
Open access, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.15260#.XpbcH96IXqs
 
Have only skimmed this, but looking at the charts, there isn't much to get excited about here. Possibly a difference between healthy controls and males with ME/CFS in two miRNAs, but considering the number of miRNAs looked at, the fairly small sample sizes, and the possibility of confounding factors, well, those two are worth looking at a bit more, but, yeah.

To get an idea, all you really need to know about the charts below is that blue are controls and red are people with ME/CFS, and these are just the results for the miRNAs showing the biggest differences:
Females:
Screen Shot 2020-04-16 at 10.01.35 AM.png
Males:
Screen Shot 2020-04-16 at 10.02.00 AM.png
 
Interesting. The two miRNA's in males that @Hutan highlights as interesting are miRNA-423-5p and miRNA-4443. Just shows you the power of ignoring the fancy words in a paper and looking at the scatter plot to see what really is interesting! I'm only able to scan the paper quickly too.......Sigh

There seems to be a fair few cancer studies looking at miRNA-423-5p. This study looks interesting - perhaps males with ME have more cell Autophagy going on (Autophagy is the body's way of cleaning out damaged cells, in order to regenerate newer, healthier cells). Could this tie in with Karl Morten and Fisher et al reporting lymphocytes in ME patients die quicker in test tubes? I wonder if they have the capability of measuring cell death rate vs miRNA-423-5p expression?

"miRNA-423-5p Promotes Autophagy in Cancer Cells and Is Increased in Serum From Hepatocarcinoma Patients Treated With Sorafenib"
https://www.sciencedirect.com/science/article/pii/S2162253116300191

miRNA-4443 seems to be related to Leptin and insulin. I seem to remember Leptin has come up in ME studies before. Anyone know if Karl Morten has looked at male vs female results on Leptin or insulin in his metabolomics studies? @Andy?

"Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells."
https://www.ncbi.nlm.nih.gov/pubmed/27842582
 
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