Introduction
The ability of immune cells to
differentiate between healthy cells and abnormal or non-self entities is
critical for efficient elimination of potentially harmful pathogens and
cells. However, maintaining self-tolerance while preserving defensive
immune responses is a complex process that can be disrupted in certain
individuals. This can lead to chronic infections or cancers in
immunocompromised individuals or autoimmune diseases in those who fail
to maintain immunological tolerance to self-antigens. Over 100 chronic
inflammatory or autoimmune diseases have been cataloged, affecting
5-10% of the general population[1]. Ankylosing
spondylitis (AS) is the most common arthritic condition affecting the
spine, characterized by bone spur formation, back pain, spinal fusion,
and disability[2]. AS is driven by disseminated
inflammation throughout the skeletal system, which leads to new bone
formation that underlies the pathological outcomes observed in AS
patients[3].
RNA species play diverse roles in
cells, and non-coding RNAs (ncRNAs) with distinct functions have been
identified, including circular RNAs (circRNAs)[4,
5]. Although generally classified as ncRNAs, certain circRNAs have
been shown to yield polypeptides[6, 7]. CircRNAs
often harbor miRNA response elements (MREs) and can function as
competing endogenous RNAs (ceRNAs) to suppress miRNA
functionality[8, 9]. CircRNAs are crucial
regulators of gene expression and have been implicated in a range of
pathological processes[10], including cancer,
autoimmunity, and diseases of the nervous and cardiovascular
systems[11-13]. Autoimmune conditions such as
systemic lupus erythematosus (SLE)[14, 15],
multiple sclerosis (MS) [16], rheumatoid arthritis
(RA)[17, 18], primary biliary cholangitis
(PBC)[19], and osteoarthritis
(OA)[20, 21] have been shown to be regulated by
circRNAs. Thus, to study their specific roles in the context of AS has
the potential to yield important insights into the disease’s underlying
mechanisms and possible therapeutic targets.
The aim of this study was to identify circRNAs that act as ceRNAs
(ceRNAs) and play critical functional roles in AS. High-throughput
RNA-sequencing (RNA-seq) analyses of peripheral blood mononuclear cells
(PBMCs) from AS patients and healthy controls were used to identify
differentially expressed circRNAs (DECs) associated with AS. Together,
these findings will provide novel insights into the role of circRNAs in
the regulation of AS.