This comprehensive exploration delves into the pivotal role of microRNAs (miRNAs) within the intricate tapestry of cellular regulation. As potent orchestrators of gene expression, miRNAs exhibit diverse functions in cellular processes, extending their influence from the nucleus to the cytoplasm. The complex journey of miRNA biogenesis, involving transcription, processing, and integration into the RNA-induced silencing complex, showcases their versatility. In the cytoplasm, mature miRNAs finely tune cellular functions by modulating target mRNA expression, while their reach extends into the nucleus, influencing transcriptional regulation and epigenetic modifications. Dysregulation of miRNAs becomes apparent in various pathologies, such as cancer, autoimmune diseases, and inflammatory conditions. The adaptability of miRNAs to environmental signals, interactions with transcription factors, and involvement in intricate regulatory networks underscore their significance. DNA methylation and histone modifications adds depth to understanding the dynamic regulation of miRNAs. Mechanisms like competition with RNA-binding proteins, sponging, and the control of miRNA levels through degradation and editing contribute to this complex regulation process. In this review, we mainly focus on how dysregulation of miRNA expression can be related with skin-related autoimmune and autoinflammatory diseases, arthritis, cardiovascular diseases, inflammatory bowel disease, autoimmune and autoinflammatory diseases, and neurodegenerative disorders. We also emphasize the multifaceted roles of miRNAs, urging continued research to unravel their complexities. The mechanisms governing miRNA functions promise advancements in therapeutic interventions and enhanced insights into cellular dynamics in health and disease.

MicroRNAs (miRNAs) are small non‐protein‐coding RNAs which are essential regulators of host genome expression at the post‐transcriptional level. There is evidence of dysregulated miRNA expression patterns in a wide variety of diseases, such as autoimmune and inflammatory conditions. These miRNAs have been termed “inflammamiRs.” When working with miRNAs, the method followed, the approach to treat or diagnosis, and the selected biological material are very crucial. Demonstration of the role of miRNAs in particular disease phenotypes facilitates their evaluation as potential and effective therapeutic tools. A growing number of reports suggest the significant utility of miRNAs and other small RNA drugs in clinical medicine. Most miRNAs seem promising therapeutic options, but some features associated with miRNA therapy like off‐target effect, effective dosage, or differential delivery methods, mainly caused by the short target's sequence, make miRNA therapies challenging. In this review, we aim to discuss some of the inflammamiRs in diseases associated with inflammatory pathways and the challenge of identifying the most potent therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics. We also discuss the status of inflammamiRs in clinical trials.

Telocytes have some cytoplasmic extensions called telopodes, which are thought to play a role in mitochondrial transfer in intercellular communication. Besides, it is hypothesized that telocytes establish cell membrane-mediated connections with breast cancer cells in coculture and may contribute to the survival of neoplastic cell clusters together with other stromal cells. The aim of this study is to investigate the contribution of telocytes and telocyte-derived mitochondria, which have also been identified in breast tumors, to the tumor development of breast cancer stem cells (CSCs) via miR-146a-5p. The isolation/characterization of telocytes from bone marrow mononuclear cells and the isolation of mitochondria from these cells were performed, respectively. In the next step, CSCs were isolated from the MDA-MB-231 cell line and were characterized. Then, miR-146a-5p expressions of CSCs were inhibited by anti-miR-146a-5p. The epithelial-mesenchymal transition (EMT) was determined by evaluating changes in vimentin protein levels and was evaluated by analyzing BRCA1, P53, SOX2, E-cadherin, and N-cadherin gene expression changes. Our results showed that miR-146a promoted stemness and oncogenic properties in CSCs. EMT (N-cadherin, vimentin, E-cadherin) and tumorigenic markers (BRCA1, P53, SOX2) of CSCs decreased after miR-146a inhibition. Bone marrow-derived telocytes and mitochondria derived from telocytes favored the reduction of CSC aggressiveness following this inhibition.

Background/Aims: Familial Mediterranean fever (FMF) is an autosomal recessive inflammasomopathy caused by mutations in the MEditerranean FeVer (MEFV) gene and is characterized by recurrent inflammatory attacks largely associated with pyrin inflammasome activity. Although FMF is a monogenic disease, clinical heterogeneity suggests the contribution of additional regulatory mechanisms, including epigenetic factors such as microRNAs (miRNAs). Previous studies identified miR-197-3p as a regulator of inflammatory signaling by targeting IL1R1. The objective of this study was to investigate the functional role of miR-197-3p in pyrin inflammasome activation and priming mechanisms in macrophages derived from an FMF knock-in mouse model. Materials and Methods: Bone marrow–derived macrophages (BMDMs) from MefvV726A/V726A mice were transfected with pre–miR-197-3p or a mimic control. Following transfection, inflammasome priming and activation were induced using specific inflammasome activators and Toll-like receptor (TLR) agonists targeting pyrin, AIM2, and NOD-like receptor protein 3 pathways. Interleukin-1β (IL-1β) secretion and pro–IL-1β expression were subsequently assessed. Results: Overexpression of miR-197-3p significantly reduced IL-1β secretion following just pyrin inflammasome activation, while responses mediated by other inflammasome pathways were largely preserved. In addition, miR- 197-3p overexpression was associated with decreased pro–IL-1β expression in response to TLR2 stimulation. Conclusion: These findings suggest that miR-197-3p may preferentially influence pyrin inflammasome–related inflammatory responses in FMF macrophages. While the present data do not establish a direct mechanistic interaction, they support a potential regulatory role for miR-197-3p in FMF-associated inflammation and provide a basis for future mechanistic and in vivo studies. Cite this article as: Ulum YZA, Sen B, Akbaba TH, Peynircioglu BB. Modulation of inflammasome activity by miR-197-3p in familial Mediterranean fever mouse macrophages. Arch Rheumatol. 2026;41(2):144-152.