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INNOSC Theranostics and
            Pharmacological Sciences                                              Transcriptome-based RNA sequencing



            and immunological function. The pathological foundation   with DNA sequences and genetic variants. Combining
            of RA is synovitis, and a variety of inflammatory responses   these disparate omics datasets can enable researchers to
            have been observed in the synoviums of patients with RA   obtain a more detailed knowledge of intricate biological
            (the soft tissue lining the interior of joints, tendon sheaths,   processes and illnesses such as RA. A more comprehensive
            and bursae is known as the synovium, also known as the   understanding of the molecular mechanisms underlying
            synovial membrane or stratum synoviale). By suppressing   the pathophysiology of RA is possible through integration,
            JAK2 and STAT1, RA can be treated by activating T and B   which enables the investigation of interactions and
            cells and preventing the production of cytokines. 74  correlations  between  genes,  proteins,  metabolites,  and
              The pathogenic process of RA is intimately associated   epigenetic variables. 79,80  RA is a mixed disease involving
            with the MAPK signaling system. The most significant   numerous biological processes, including inflammation
            member of the MAPK family, P38 MAPK, is activated in   dysregulation and tissue damage. Multiomics approaches
            endogenous immune cells and can thicken the synovium,   allow an in-depth overview of the molecular landscape
            activate transcription factors, and significantly increase   by continuously analyzing multiple biological layers of
            the production of inflammatory chemokines. It may also   bio information such as transcriptomics and genomics.
            contribute to T-cell differentiation and prevent cell death.   RA exhibits a diverse clinical presentation and response
            Angiogenesis, proliferation, metabolism, and cell survival   to treatment.  Mutiomics  data help  identify  molecular
            are all regulated by the PI3K-AKT pathway, an intracellular   subtypes  or  clusters  within  patients,  which  helps  in  the
            mechanism that has been associated with the onset and   treatment of particular individuals. Multiomics data
            progression of RA. The pathophysiology of RA is aided by   help interconnect molecular pathways and networks and
            the abnormal activation of this pathway, which increases   identify signaling pathways driving disease progression.
            the production of inflammatory chemicals and cytokines. 75  Multiomics  helps discover  and develop  new  therapeutic
                                                               agents  for  patients  with  RA.  Researchers  can  repurpose
              In the PI3K/AKT/mTOR pathway, the mammalian target
            of rapamycin (mTOR) suppresses autophagy, encourages   current medications with established effects on relevant
                                                               molecular pathways and prioritize prospective targets for
            aberrant synovial cell proliferation, and is essential
            for osteoclast survival and differentiation, all of which   therapeutic development by identifying molecular targets
                                                                                                     81,82
            exacerbate RA. SYK and BTK are two important molecules   and pathways implicated in the disease etiology.
            involved in B-cell receptor signaling, whose dysregulation   8. Benefits, limitations, and significant
            has been linked to the etiology of RA. Phosphorylated SYK
            and BTK are expressed at higher levels in peripheral B cells   advances of the technique
            in patients with RA, which is associated with the formation   Several simple and complex diseases are poorly
            of autoantibodies. Regarding the treatment for autoimmune   understood; hence, the  analysis of  their  transcriptome
            conditions such as RA, BTK is a desirable target. 75  is a vital method to investigate various diseases such
              By controlling bone metabolism and synovial      as RA. Next-generation RNA-seq is a high-throughput
            inflammation, the Wnt signaling pathway is essential in the   method for the characterization of gene expression levels.
            pathophysiology of RA. Studies have demonstrated that the   Therefore, the use of RNA-seq in RA research has several
            inhibition of NAV2 expression stops the development of   benefits. This method can detect all RNA transcripts
            RA and reverses phenotypes associated with inflammation,   irrespective  of  the  genes  known  or  presently  unknown,
            making it a prospective target for RA therapy. 74,75  which provides a better view of the gene changes occurring
                                                               in RA. RNA-seq provides precise and quantitative
            7. Integration of multiomics data to clarify       readouts of gene expression, therefore making it possible
            the molecular mechanisms underlying RA             to capture differences in gene expression kinetics. It can
                                                               also capture cases of alternative splicing, which results in
            The term “multiomics data” describes the synthesis of   the production of different proteins that are functionally
            several types of molecular data from different omics   different. RNA-seq can also identify unidentified RNA
            technologies, including transcriptomics, proteomics,   forms, for instance, ln cRNA and miRNA, which are
            metabolomics, and epigenomics. 76-78  Every omics technique   responsible for the regulation of gene expressions. RNA-
            provides a limited perspective on the various facets of   seq data obtained from RA samples can be combined with
            biological systems. Proteomics investigates proteins and   other omics data, including genomics and proteomics data,
            their  alterations,  metabolomics  explores  small  molecule   to further investigate the pathogenesis of RA.
            metabolites, transcriptomics examines gene expression
            levels, and epigenomics investigates epigenetic changes that   Nevertheless, at the same time, there are some limitations
            control gene expression. Genomics is primarily concerned   to using RNA-seq. For instance, when performing large-


            Volume 8 Issue 1 (2025)                         26                               doi: 10.36922/itps.4449
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