Mechanisms and application strategies of miRNA‑146a regulating inflammation and fibrosis at molecular and cellular levels (Review)

Abstract

In the progression of various diseases, inflammation has a critical role. Chronic persistent inflammation is a pivotal trigger of fibrosis. Several microRNAs (miRNAs) participate in inflammation and fibrosis. In recent years, it has been proved that miRNAs are a critical link in physiological and pathological processes. Among them, the miRNA miR-146a has a pivotal role in the immune system and acquired immunity, making it one of the most studied miRNAs. Due to its essential roles at the molecular and cellular levels, it has broad application prospects in precision medicine. The present comprehensive review focused on the mechanisms of miR-146a and its application strategies in inflammation and fibrosis, discussing its therapeutic potential. The main signaling pathways through which miR-146a regulates inflammation and fibrosis and their relationships were covered. Furthermore, the functions and effects of miR-146a in specific cells, which may join in the process of inflammation and fibrosis, were outlined. Application strategies were also summarized according to recent studies based on these mechanisms. Contents 1. Introduction 2. Location and transcription regulation of miR-146a 3. miR-146a and inflammation 4. miR-146a and fibrosis 5. Application strategies 6. Conclusions and perspectives

EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells

“…However, overexpression of miR-146a-5p in mimic transfected cells resulted in increased accumulation of TGFb, suggesting that miR-146a-5p increases EMMPRIN that in turn enhances TGFb. Moreover, it also provides a mechanistic explanation to the link previously found between miR-146a-5p and the EMT process (71). Conversely, TRAF6 is a well-known target of miR-146a-5p but not of EMMPRIN, and therefore its reduced expression in CT26-WT-mimic cells relative to the negative control is of no surprise.…”

Association of MicroRNA-146a expression level and it’s Gene Polymorphism rs2910164 C/G in patients with Rheumatoid Arthritis

“…Individuals bearing the G/C versus G/G genotype in the Iranian population, as well as the G/C + C/C versus G/G genotype in females alone rather than males, are at risk of getting RA [29]. The rs2910164 polymorphism had a direct functional effect on miR-146a's ability to inhibit its target genes TRAF6 and IRAK1 [30]. Given that TRAF6 and IRAK1 have been linked to RA pathogenesis, this polymorphism may play a role in RA development [28]…”

Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review

“…Inflammatory cytokines are the main mediators implicated in the activation of coagulation. Therefore, it is not surprising that a decreased level of miRNA-146a and an associated activation of the aforementioned inflammatory cascade increases the risk of major cardiovascular events (MACE) [45,56,85], especially AIS. The molecular pathway of miRNA-146a in AIS in the brain responds via the same kinases or transcription factors as in the heart.…”