High-Throughput Sequencing of Plasma MicroRNA in CFS/ME, 2014, Brenu, Staines, Marshall-Gradisnik et al

Hutan · Jun 25, 2023

Ekua W. Brenu ,Kevin J. Ashton,Jana Batovska,Donald R. Staines,Sonya M. Marshall-Gradisnik

Abstract
Background
MicroRNAs (miRNAs) are known to regulate many biological processes and their dysregulation has been associated with a variety of diseases including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The recent discovery of stable and reproducible miRNA in plasma has raised the possibility that circulating miRNAs may serve as novel diagnostic markers. The objective of this study was to determine the role of plasma miRNA in CFS/ME.

Results
Using Illumina high-throughput sequencing we identified 19 miRNAs that were differentially expressed in the plasma of CFS/ME patients in comparison to non-fatigued controls. Following RT-qPCR analysis, we were able to confirm the significant up-regulation of three miRNAs (hsa-miR-127-3p, hsa-miR-142-5p and hsa-miR-143-3p) in the CFS/ME patients.

Conclusion
Our study is the first to identify circulating miRNAs from CFS/ME patients and also to confirm three differentially expressed circulating miRNAs in CFS/ME patients, providing a basis for further study to find useful CFS/ME biomarkers.

https://pubmed.ncbi.nlm.nih.gov/25238588/

Hutan · Jun 25, 2023

Fukuda criteria; six CFS/ME and six healthy controls (chosen from 20 CFS/ME and 20 controls on the basis of having produced the most small rna after plasma processing); no adjustment for false discovery rate

So, it's a really small sample, as is so often the way with the NCNED work. Also the six CFS/ME participants had differences in blood cell percentages (higher % of granulocytes; lower percentage of lymphocytes) compared to the the 20 ME/CFS sample and to the 6 controls - so they may well not be representative of ME/CFS participants.

A total of 375 mature miRNA were initially identified in one or more samples based on sequence alignment to the miRBase registry
Click to expand...

A total of 19 microRNAs were significantly dysregulated in CFS/ME compared to non-fatigued controls (Table 4). Of the 19 differentially expressed miRNAs 16 were considered low in abundance due to a base mean count of less than 1,000 reads, their detection was found to be unreliable for confirmative RT-qPCR.The remaining three miRNAs (hsa-miR127-3p, hsa-miR-142-5p and hsa-miR-143-3p) were all up-regulated in CFS/ME compared to non-fatigued controls.
Click to expand...

Over-expression of miR-142-5p has been observed in most cancer-related and immunological disorders [39]. This particular miRNA is abundant in most hematopoietic cell lines and may be involved in thwarting inflammatory processes [40]. In Systemic Lupus Erythematosus (SLE), increased expression of miR-142-5p in CD4+T cells prevents autoimmunity while a downregulation may result in autoreactive T cells and hyperactive B cells [41]

MiR-142-5p is important for T cell development where it targets SLAM associate protein (SAP). Inhibition of miR-142-5p may increase the expression of CD84, IL-10, SAP and IgG production [41]. CD84 is an important T cell regulatory marker as it regulates cytokine production, function, adhesion and interaction with B cells [42]. The levels of IL-10 have been shown to be equivocal in CFS/ME patients. The cause of an increase in miR-142-5p is unknown, however, it is likely that this may be related to heightened Treg suppression and additional autoimmune responses.

MiR-143-3p targets IgG Fcγ receptor 1 and also CD64 reducing lung inflammation. It is a tumour suppressor gene and is highly down regulated in colorectal cancer [43]. It inhibits the oncogene KRAS [44]. Overexpression of miR-143-3p in most cancer cells stagnates the growth of tumours and cancer cells [45] as it may act to reduce BCL2 mRNA thereby preventing tumour or cancer cell proliferation and promoting apoptosis [46]. miR-143-3p has been identified as a neutrophil specific miRNA [47]. Importantly, its expression is upregulated in cases of heightened erythropoiesis such as in polycythemia [48]. In CFS/ME increased levels of neutrophil apoptosis occurs in some patients [49], [50], [51], and this potentially ensues from high levels of miR-143-3p.

MiR-127-3p interferes with ERK signalling, a tumour suppressor and upregulations have been shown to increase apoptosis [52]. Importantly, it targets BCL6 a transcription factor which increases p53 expression [53]. BCL6 inhibits the production of IL-10 therefore by dampening BCL6 as a consequence of miR-127upregulation may result in significant increases in IL-10 [54]. In CFS/ME equivocal levels of IL-10 have been reported and an over expression of miR-127-3p may explain to some extent some of these patterns. BCL6 is an important transcription factor required for germinal centre B cell and follicular helper T cell development [55], [56], [57]. Irregularities in the expression of BCL6 may result in aberrant inflammatory responses and the development of various lymphomas [58].
Click to expand...

DokaGirl · Jun 25, 2023

Hutan said: ↑

View attachment 19771

Fukuda criteria; six CFS/ME and six healthy controls (chosen from 20 CFS/ME and 20 controls on the basis of having produced the most small rna after plasma processing); no adjustment for false discovery rate

So, it's a really small sample, as is so often the way with the NCNED work. Also the six CFS/ME participants had differences in blood cell percentages (higher % of granulocytes; lower percentage of lymphocytes) compared to the the 20 ME/CFS sample and to the 6 controls - so they may well not be representative of ME/CFS participants.
Click to expand...

It seems the ME/CFS participants may be doubly unpresentative of pwME given the choice to use Fukuda criteria, and the differences in blood cell percentages.

Log in or Sign up

High-Throughput Sequencing of Plasma MicroRNA in CFS/ME, 2014, Brenu, Staines, Marshall-Gradisnik et al

Hutan Moderator Staff Member

Hutan Moderator Staff Member

DokaGirl Senior Member (Voting Rights)

Share This Page

Log in or Sign up

High-Throughput Sequencing of Plasma MicroRNA in CFS/ME, 2014, Brenu, Staines, Marshall-Gradisnik et al

Hutan Moderator Staff Member

Hutan Moderator Staff Member

DokaGirl Senior Member (Voting Rights)

Share This Page

Useful Searches