A unique circular RNA expression pattern in the peripheral blood of myalgic encephalomyelitis/chronic fatigue syndrome patients

Yuning Cheng; Si-Mei Xu; Konii Takenaka; Grace Lindner; Ashton Curry-Hyde; Michael Janitz

doi:10.1016/j.gene.2023.147568

A unique circular RNA expression pattern in the peripheral blood of myalgic encephalomyelitis/chronic fatigue syndrome patients

Gene. 2023 Aug 15:877:147568. doi: 10.1016/j.gene.2023.147568. Epub 2023 Jun 15.

Authors

Yuning Cheng¹, Si-Mei Xu¹, Konii Takenaka¹, Grace Lindner¹, Ashton Curry-Hyde¹, Michael Janitz²

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
² School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Paul Flechsig Institute of Brain Research, University of Leipzig, 04103 Leipzig, Germany. Electronic address: m.janitz@unsw.edu.au.

PMID: 37328077
DOI: 10.1016/j.gene.2023.147568

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with obscure aetiology. The underdiagnosis rate of ME/CFS is high due to the lack of diagnostic criteria based on objective markers. In recent years, circRNAs have emerged as potential genetic biomarkers for neurological diseases, including Parkinson's disease and Alzheimer's disease, making them likely to have the same prospect of being biomarkers in ME/CFS. However, despite the extensive amount of research that has been performed on the transcriptomes of ME/CFS patients, all of them are solely focused on linear RNAs, and the profiling of circRNAs in ME/CFS has been completely omitted. In this study, we investigated the expression profiles of circRNAs, comparing ME/CFS patients and controls before and after two sessions of cardiopulmonary exercise longitudinally. In patients with ME/CFS, the number of detected circRNAs was higher compared to healthy controls, indicating potential differences in circRNA expression associated with the disease. Additionally, healthy controls showed an increase in the number of circRNAs following exercise testing, while no similar pattern was evident in ME/CFS patients, further highlighting physiological differences between the two groups. A lack of correlation was observed between differentially expressed circRNAs and their corresponding coding genes in terms of expression and function, suggesting the potential of circRNAs as independent biomarkers in ME/CFS. Specifically, 14 circRNAs were highly expressed in ME/CFS patients but absent in controls throughout the exercise study, indicating a unique molecular signature specific to ME/CFS patients and providing potential diagnostic biomarkers for the disease. Significant enrichment of protein and gene regulative pathways were detected in relation to five of these 14 circRNAs based on their predicted miRNA target genes. Overall, this is the first study to describe the circRNA expression profile in peripheral blood of ME/CFS patients, providing valuable insights into the molecular mechanisms underlying the disease.

Keywords: Chronic fatigue syndrome; Circular transcriptome profiling; Differential expression; Myalgic encephalomyelitis; circular RNAs.

MeSH terms

Fatigue Syndrome, Chronic* / diagnosis
Fatigue Syndrome, Chronic* / genetics
Gene Expression Regulation
Genetic Markers
Humans
RNA, Circular / genetics

Substances

RNA, Circular
Genetic Markers