Implications and theragnostic potentials of circular RNAs in rheumatic diseases

Abbas, Alaa Ahmed; Abdulkader, Hadil Adnan; Giordo, Roberta; Erre, Gian Luca; Pintus, Gianfranco; Zayed, Hatem

doi:10.1016/j.ijbiomac.2023.123783

Cited by 4 publications

(2 citation statements)

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“…CircRNAs, which are a type of closed circular non-coding RNAs (ncRNAs) connected by covalent bonds and possess a relatively stable structure, play a crucial role in the progression of various diseases by targeting specific genes and regulating cellular metabolism [ 13 ]. The involvement of circRNAs in RA has garnered significant attention.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast-like synoviocytes-derived exosomal circFTO deteriorates rheumatoid arthritis by enhancing N6-methyladenosine modification of SOX9 in chondrocytes

Li,

Fang,

et al. 2024

Arthritis Res Ther

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Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes disability worldwide. Exosomes released by fibroblast-like synoviocytes in RA (RA-FLSs-Exos) play a role in the development of RA, and circular RNAs (circRNAs) are important for RA progression. This study aimed to investigate the molecular mechanisms underlying the effects of RA-FLSs-Exos in RA and identify the potential pathway responsible for these effects. Methods We initially conducted microarray analysis to identify dysregulated circRNAs in exosomes associated with RA. We then co-cultured isolated RA-FLSs-Exos with chondrocytes to examine their role in RA. In vivo experiments were performed using collagen-induced arthritis mouse models, and circFTO knockdown was achieved through intra-articular injection of AAV5 vectors. Results Our findings revealed increased expression of circFTO in both RA-FLSs-Exos and synovial tissues from patients with RA. Exosomal circFTO hindered chondrocyte proliferation, migration, and anabolism while promoting apoptosis and catabolism. Mechanistically, we discovered that circFTO facilitates the formation of methyltransferases complex to suppress SRY-related high-mobility group box 9 (SOX9) expression with assistance from YTH domain family 2 (YTHDF2) through an m6A-dependent mechanism. Furthermore, inhibition of circFTO improved symptoms of RA in vivo. Conclusion Taken together, our study demonstrates that exosomal circFTO derived from FLSs contributes to the progression of RA by targeting SOX9. These findings highlight a promising target for treating RA.

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Section: Introductionmentioning

confidence: 99%

Fibroblast-like synoviocytes-derived exosomal circFTO deteriorates rheumatoid arthritis by enhancing N6-methyladenosine modification of SOX9 in chondrocytes

Li,

Fang,

et al. 2024

Arthritis Res Ther

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“…CircRNAs do not have any free 5′ and 3′ ends in their structure, making them resistant to exoribonucleases; hence, their transcripts are very stable and conserved. CircRNA dysregulation is also associated with several diseases including cancer, neurological problems, cardiovascular, and rheumatic diseases (He et al 2021 ; Almaghrbi et al 2023 ; Abbas et al 2023 ). Disease-linked variations in the expression of many circRNAs may make them potential biomarkers for several complex human diseases.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic and diagnostic applications of exosomal circRNAs in breast cancer

Gopikrishnan

Ramanathan

et al. 2023

Funct Integr Genomics

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Circular RNAs (circRNAs) are regulatory elements that are involved in orchestrating gene expression and protein functions and are implicated in various biological processes including cancer. Notably, breast cancer has a significant mortality rate and is one of the most common malignancies in women. CircRNAs have been demonstrated to contribute to the pathogenesis of breast cancer including its initiation, progression, metastasis, and resistance to drugs. By acting as miRNA sponges, circRNAs can indirectly influence gene expression by disrupting miRNA regulation of their target genes, ultimately altering the course of cancer development and progression. Additionally, circRNAs can interact with proteins and modulate their functions including signaling pathways involved in the initiation and development of cancer. Recently, circRNAs can encode peptides that play a role in the pathophysiology of breast cancer and other diseases and their potential as diagnostic biomarkers and therapeutic targets for various cancers including breast cancer. CircRNAs possess biomarkers that differentiate, such as stability, specificity, and sensitivity, and can be detected in several biological specimens such as blood, saliva, and urine. Moreover, circRNAs play an important role in various cellular processes including cell proliferation, differentiation, and apoptosis, all of which are integral factors in the development and progression of cancer. This review synthesizes the functions of circRNAs in breast cancer, scrutinizing their contributions to the onset and evolution of the disease through their interactions with exosomes and cancer-related intracellular pathways. It also delves into the potential use of circRNA as a biomarker and therapeutic target against breast cancer. It discusses various databases and online tools that offer crucial circRNA information and regulatory networks. Lastly, the challenges and prospects of utilizing circRNAs in clinical settings associated with breast cancer are explored.

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