Expression, Regulation and Function of MicroRNAs in Multiple Sclerosis

Abstract

MicroRNAs (miRNAs) are single-stranded 19-25 nucleotide-long RNAs and have an important role in post-transcriptional gene silencing. It has been demonstrated that miRNAs are dysregulated in patients with multiple sclerosis (MS). For instance, miR-21, miR-142-3p, miR-146a, miR-146b, miR-155 and miR-326 were up-regulated in both peripheral blood mononuclear cells (PBMCs) and brain white matter lesions from MS patients and mouse model as well. These up-regulated miRNAs may be used as a signature for MS and play critical roles in MS pathogenesis. Moreover, miR-15a, miR-19a, miR-22, miR-210 and miR-223 were up-regulated in both regulatory T cells (Tregs) and other samples such as plasma, blood cells, PBMCs and brain white matter tissues from MS patients, suggesting that these up-regulated miRNAs and Tregs may also play a role in MS pathogenesis. Contrarily, other miRNAs such as miR-15a, miR-15b, miR-181c and miR-328 were down-regulated in MS. Drugs such as interferon-β and glatiramer acetate for MS treatment may regulate miRNA expression and thus have benefits for MS patients. The dysregulated miRNAs such as miR-155 and miR-326 may be used as diagnostic markers and therapeutic targets for MS.

Longitudinal Examination of the Intestinal Lamina Propria Cellular Compartment of Simian Immunodeficiency Virus-Infected Rhesus Macaques Provides Broader and Deeper Insights into the Link between Aberrant MicroRNA Expression and Persistent Immune Activation

“…miRNA dysregulation has been associated with several chronic inflammatory diseases, such as inflammatory bowel disease (9), experimental autoimmune encephalomyelitis (10), multiple sclerosis (11), and rheumatoid arthritis (12). Lately, the enhanced expression of miR-21 (13) and miR-142 (14) was correlated with macrophage activation and encephalitis in the brain of SIV-infected rhesus macaques.…”

Processo epigenéticos envolvidos na fisiopatologia da esclerose múltipla com ênfase na função dos miRNAs

“…De acordo com Ma et al, (2014) a disfunção da barreira hematoencefálica é associada com a patogênese da EM. A down regulation do miR125a-5p está envolvida na regulação do efluxo de células imunológicas e na permeabilidade das células endoteliais na barreira hematoencefálica, sugerindo assim que o miR-125a-5p pode desempenhar um papel fundamental na fisiopatogênese da esclerose múltipla.…”

“…Em um levantamento realizado por Ma et al (2014), foi descrito o mecanismo de ação dos miRNAs que estão desregulados em pacientes com esclerose múltipla, segundo estes os miRNAs possuem como função principal a regulação gênica de forma negativa. De acordo com esse estudo, diferentes microRNAs estariam interferindo na diferenciação dos linfócitos TCD4.…”

“…Além disto, essas moléculas são excepcionalmente estáveis em fluidos biológicos, sugerindo uma exportação das mesmas em exossomos, os quais previnem uma degradação dos miRNAs por RNases. Reforçando assim o seu potencial como um futuro biomarcador para a esclerose múltipla (MA et al,2014;ZHANG et al, 2013).…”

Large-Scale Integrative Analysis of Epigenetic Modifications Induced by Isotretinoin, Doxycycline and Metronidazole in Murine Colonic Intestinal Epithelial Cells

“…Mechanisms of transcriptional regulation that do not alter the sequence of DNA are called epigenetic regulations and have been studied extensively over the last few years. These studies have shown that epigenetics play a relevant role in a variety of diseases, e.g., IBD [4,5], multiple sclerosis [6], psoriasis [7] and systemic lupus erythematosus (SLE) [8]. Importantly, epigenetic marks may persist through cell division and are inheritable to next generations (long-term effects) [9].…”