Identification of a circulating miRNA signature in extracellular vesicles collected from amyotrophic lateral sclerosis patients

Shan

et al. 2019

Preprint

Background Atherosclerosis (AS) is a multifactorial chronic disease, and vascular smooth muscle cells (VSMCs) plays an important role in the pathology of AS. MicroRNAs regulate multiple cellular biological processes. This study aimed to investigate the clinical value of miR-183-5p in AS patients, and further explored the effects of miR-183-5p on the proliferation and migration of VSMCs. Methods qRT-PCR was used to test the level of miR-183-5p. The diagnostic value of miR-183-5p for AS patients was assessed by a receiver operating characteristic (ROC) analysis. Cell proliferation and migration were determined via CCK-8 and Transwell assay. Results MiR-183-5p was highly expressed in AS patients compared with the healthy group. Serum miR-183-5p expression was positively associated with CIMT and CRP in AS patients. The ROC analysis suggested that miR-183-5p had quality to be used as a biomarker with high specificity and sensitivity for AS detection. Overexpression of miR-183-5p promoted the proliferation and migration of VSMCs. Downregulation of miR-183-5p attenuated ox-LDL stimulated VSMCs proliferation and migration. Conclusion MiR-183-5p is highly expressed in AS patients, and downregulation of miR-183-5p attenuated ox-LDL stimulated VSMCs proliferation and migration. MiR-183-5p may be a key molecular for the diagnosis and treatment of AS in the future.

Section: Discussionmentioning

confidence: 99%

MicroRNA-183-5p acts as a potential diagnostic biomarker for atherosclerosis and regulates the growth of vascular smooth muscle cell

Shan

et al. 2019

Preprint

“…miR-338-3p is another potential circulating miRNA for ALS, since it was found consistently upregulated in several studies [45,50,111,114,121,126]. Its role as a functional miRNA in controlling different molecular pathways has been reported.…”

Section: The Most Promising Potential Circulating Mirna Biomarkers Anmentioning

confidence: 98%

“…All the above described studies used as an miRNA detection approach combination of microarrays and qRT-PCR or qRT-PCR alone, however in three most recent studies, high-throughput next-generation RNA sequencing was applied [45,67,126].…”

Section: Mirnas As Candidate Circulating Biomarkers Of Alsmentioning

confidence: 99%

“…Deregulated miRNAs most relevant to ALS included miR-9-5p, miR-183-5p, miR-338-3p and miR-1246. miR-15a-5p was identified for its diagnostic potential and miR-193a-5p for disability progression [126].…”

Section: Mirnas As Candidate Circulating Biomarkers Of Alsmentioning

confidence: 99%

“…miR-183 was found dysregulated in peripheral blood samples of sporadic ALS patients in three different studies [67,118,126]. miR-183 family (including miR-183, miR-96 and miR-182) are highly conserved miRNAs with many revealed roles in different cancers, immunity and nervous system [143][144][145][146][147].…”

Section: The Most Promising Potential Circulating Mirna Biomarkers Anmentioning

confidence: 99%

See 2 more Smart Citations

Circulating RNAs as Potential Biomarkers in Amyotrophic Lateral Sclerosis

Ravnik‐Glavač

Glavač

2020

IJMS

Amyotrophic lateral sclerosis (ALS) is a complex multi-system neurodegenerative disorder with currently limited diagnostic and no therapeutic options. Despite the intense efforts no clinically applicable biomarkers for ALS are yet established. Most current research is thus focused, in particular, in identifying potential non-invasive circulating biomarkers for more rapid and accurate diagnosis and monitoring of the disease. In this review, we have focused on messenger RNA (mRNA), non-coding RNAs (lncRNAs), micro RNAs (miRNAs) and circular RNA (circRNAs) as potential biomarkers for ALS in peripheral blood serum, plasma and cells. The most promising miRNAs include miR-206, miR-133b, miR-27a, mi-338-3p, miR-183, miR-451, let-7 and miR-125b. To test clinical potential of this miRNA panel, a useful approach may be to perform such analysis on larger multi-center scale using similar experimental design. However, other types of RNAs (lncRNAs, circRNAs and mRNAs) that, together with miRNAs, represent RNA networks, have not been yet extensively studied in blood samples of patients with ALS. Additional research has to be done in order to find robust circulating biomarkers and therapeutic targets that will distinguish key RNA interactions in specific ALS-types to facilitate diagnosis, predict progression and design therapy.

Biomarker Organization in Circulating Extracellular Vesicles: New Applications in Detecting Neurodegenerative Diseases

2020

These tests, which assess different aspects of the patients' cognitive abilities, include abbreviated mental test (AMT), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), mini mental state examination (MMSE), the Montreal cognitive assessment (MoCa), and short blessed test (SBT). Such assessments, however, are subjective and detect diseases only at a late stage. [3-5] As pathological manifestations of neurodegenerative diseases are mainly confined within the brain and difficult to access, alternative methods for evaluating disease pathology involve either invasive biopsy or expensive brain imaging; these approaches are complex and challenging, resulting in limited clinical adoption. [6,7] Consequently, there is an intense interest in developing blood-based measurements [8-11] for safe, minimally invasive disease detection and longitudinal monitoring. Extracellular vesicles (EVs) are nanoscale membrane vesicles found abundantly in almost all bodily fluids. [12,13] These vesicles have recently emerged as a promising circulating biomarker for neurodegenerative diseases. Unlike most of the other molecules in the brain, which are impeded by the highly selective blood-brain barrier and cannot enter the circulation, recent studies have found that EVs can readily cross the blood-brain barrier. [14-17] Moreover, EVs contain diverse molecular contents reflective of their parent cells and extracellular environment. [18-20] These EV molecular cargoes are present in different organizational forms-either as inherited constituents from the parent Neurodegenerative diseases are heterogeneous disorders characterized by a progressive loss of function and/or death of nerve cells, leading to severe cognitive and functional decline. Due to the complex pathology, early detection and intervention are critical to the development of successful treatments; however, current diagnostic approaches are limited to subjective, late-stage clinical findings. Extracellular vesicles (EVs) have recently emerged as a promising circulating biomarker for neurodegenerative diseases. Actively released by diverse cells, EVs are nanoscale membrane vesicles. They abound in blood, readily cross the blood-brain barrier, and carry diverse molecular cargoes in different organizational states: these molecular cargoes are inherited from the parent cells or bound to the EV membrane through surface associations. Specifically, EVs have been found to be associated with several important pathogenic proteins of neurodegenerative diseases, and their involvement could alter disease progression. This article provides an overview of EVs as circulating biomarkers of neurodegenerative diseases and introduces new technological advances to characterize the biophysical properties of EV-associated biomarkers for accurate, blood-based detection of neurodegenerative diseases.