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INNOSC Theranostics and
Pharmacological Sciences Transcriptome-based RNA sequencing

pathogenic feature. Finally, these disorders result in bone It identifies genes that are upregulated or downregulated,
and cartilage dysfunction as well as stiff joints. 55,56 RA is a allowing researchers to evaluate gene expression levels and
severe inflammatory autoimmune disease that is affected identify coding and non-coding RNAs linked to RA. This
by both hereditary and environmental factors. In recent information can be used for prognosis, therapy response
years, new genes and the close relationship between genetic monitoring, and disease diagnosis. RNA-seq also profiles
and epigenetic processes have received considerable gene expression in specific cell types, helping in targeted
attention. Serological testing (rheumatoid factor and therapeutic development and drug discovery. 51,68,69
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anticyclic citrullinated peptide) and magnetic resonance
imaging are the most frequently used techniques for the 6.2. Dysregulated gene expression in RA
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early detection and diagnosis of RA. Nevertheless, these RA is caused by dysregulated gene expression, resulting
methods have limitations, and therefore, the precision and in inflammatory and autoimmune processes that damage
accuracy are poor. X-rays and computed tomography joints. Dysregulated genes produce proinflammatory
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can only identify lesions that are advanced in the stage; cytokines, causing synovial inflammation, cartilage
they cannot identify early damage. At present, there is degradation, and bone erosion. Autoantibodies and
no established therapy for RA, and its origin remains immune complexes cause tissue damage and synovial
unknown. An increasing number of studies indicate that inflammation. Dysregulated transcription factors and
it is associated with genetics, immunological problems, abnormal signaling networks promote inflammation and
endocrine variables, environment, and other factors, immune cell activation. Anti-inflammatory mediators
resulting in long-term inflammatory joint lesions. The such as TIMPs and IL-10 balance proinflammatory and
recurrence and continuation of numerous complicated anti-inflammatory responses. Identifying these genes is
diseases or biological processes are intimately linked to vital for developing customized therapies to improve the
the DNA methylation control of gene expression. DNA prognosis of patients with RA. 4,70,71
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methylation is crucial for preserving the expression profile
unique to a given tissue, blocking the expression of foreign 6.3. Regulatory networks in RA
and viral genes, imprinting gene expression, and controlling Key transcription factors, including NF-κB, AP-1, and
chromatin stability. DNA hypermethylation often prevents STAT3, exhibit dysregulated activity in RA, as shown
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transcription factors from binding to the target area, which by RNA-seq. 72,73 In the synovium of patients with RA,
can restrict gene production; however, some studies showed these factors are critical in regulating the production
that hypermethylation can also increase gene expression. of proinflammatory cytokines, chemokines, and other
The findings still require further investigation because inflammatory mediators. Gene dysregulation in RA is
of their inconsistency. Moreover, a plethora of research affected by epigenetic modifications, including chromatin
indicates that DNA methylation could play a role in the structural alterations, DNA methylation, and histone
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onset and progression of RA. Gene expression microarrays acetylation.
have primarily been used to examine gene expression Non-coding RNAs, including long non-coding RNAs
profiles, which provides a reasonably novel approach to (lncRNAs) and microRNAs (miRNAs), have also been
exploring genes and numerous opportunities for drug-based shown to play a role in RA pathophysiology. These RNAs
molecular targeting applications. Numerous investigations possess the ability to target genes related to immunological
of RA on methylation or expression microarray data responses, inflammation, and bone/cartilage homeostasis.
profiling have been conducted in recent years, and hundreds In cRNAs interact with chromatin-modifying complexes
of differentially methylated and differentially expressed or control the expression of target genes related to
genes (DMGs) have been identified. 63-67 inflammatory signaling pathways and immunological
6. Regulatory networks and signaling responses. Moreover, circular RNAs act as microRNA
pathways revealed by RNA-seq in RA sponges, absorbing miRNAs and altering their activity
to indirectly regulate gene expression in RA-related
RA and osteoarthritis are joint diseases influenced pathways. 72,73
by genetics, nutrition, and environmental factors.
Transcriptomics and RNA sequencing can help differentiate 6.4. Signaling pathways implicated in RA
between the two by examining gene expression. 51 Numerous signal transduction pathways affect the course
of RA, and aberrant signals are frequently used as targets
6.1. Role of RNA-seq in RA research for developing medications. One of the most important
RNA-seq is a crucial technique in the study of RA, providing members of the JAK family, the JAK-STAT pathway, controls
insights into the transcriptome and molecular mechanisms. apoptosis, cell differentiation, proliferation, inflammation,

Volume 8 Issue 1 (2025) 25 doi: 10.36922/itps.4449