MiRNA-146a—A Key Player in Immunity and Diseases

Abstract

miRNA-146a, a single-stranded, non-coding RNA molecule, has emerged as a valuable diagnostic and prognostic biomarker for numerous pathological conditions. Its primary function lies in regulating inflammatory processes, haemopoiesis, allergic responses, and other key aspects of the innate immune system. Several studies have indicated that polymorphisms in miRNA-146a can influence the pathogenesis of various human diseases, including autoimmune disorders and cancer. One of the key mechanisms by which miRNA-146a exerts its effects is by controlling the expression of certain proteins involved in critical pathways. It can modulate the activity of interleukin-1 receptor-associated kinase, IRAK1, IRAK2 adaptor proteins, and tumour necrosis factor (TNF) targeting protein receptor 6, which is a regulator of the TNF signalling pathway. In addition, miRNA-146a affects gene expression through multiple signalling pathways, such as TNF, NF-κB and MEK-1/2, and JNK-1/2. Studies have been carried out to determine the effect of miRNA-146a on cancer pathogenesis, revealing its involvement in the synthesis of stem cells, which contributes to tumourigenesis. In this review, we focus on recent discoveries that highlight the significant role played by miRNA-146a in regulating various defence mechanisms and oncogenesis. The aim of this review article is to systematically examine miRNA-146a’s impact on the control of signalling pathways involved in oncopathology, immune system development, and the corresponding response to therapy.

A Comparative Analysis of MicroRNA Expression in Mild, Moderate, and Severe COVID-19: Insights from Urine, Serum, and Nasopharyngeal Samples

“…This upregulation of miR-146a played a role in promoting viral replication by inhibiting the production of interferon type I [33]. Moreover, it has been observed level of miR-146a can mitigate lung cell damage by suppressing inflammatory responses [34]. Regarding miR-21, a study by Nersisyan et al [35] demonstrated an eight-fold upregulation of miR-21-3p during lung infection caused by SARS-CoV-2.…”

Indirect influence of microRNA‐146a on the association of IL‐6 and TNF‐α genetic polymorphisms with the increased risk of hip osteoarthritis

“…It has an important role in the regulation of immune system cell differentiation, inflammatory cytokines, and various immune conditions. 8,9 MiR-146a is considered a negative regulator of the immune response through the regulation of two genes, tumor necrosis factor (TNF) receptor-related factor-6 and interleukin-1 (IL-1) receptor-related kinase-1. 10,11 The same genes are considered to cause abnormal activation of the nuclear factor (NF)-kB signaling pathway that regulates the expression of some of the inflammatory mediators such as IL-6, IL-1β, TNF-α and some metalloproteinases (matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5).…”

“…MicroRNA‐146a (miR‐146a) is a member of the miRNA family and is encoded on chromosome 5q33.3. It has an important role in the regulation of immune system cell differentiation, inflammatory cytokines, and various immune conditions 8,9 . MiR‐146a is considered a negative regulator of the immune response through the regulation of two genes, tumor necrosis factor (TNF) receptor‐related factor‐6 and interleukin‐1 (IL‐1) receptor‐related kinase‐1 10,11 .…”

Analysis of IL-17A, IL-17F, and miR-146a-5p Prior to Transplantation and Their Role in Kidney Transplant Recipients

“…In the physiological state, miR-146a-5p expression is restricted to immune cells and negatively inhibits the innate and adaptive immune response by regulating certain adapters or transcription factors, including, e.g., the signal transducer and activator of transcription 1 (STAT1) [39]. Moreover, miR-146a-5p influences gene expression through multiple signaling pathways such as TNF, NF-κB, and MEK-1/2, and JNK-1/2 [40]. The expression levels of miR-146a-5p were increased in patients with kidney diseases, with focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis [41].…”