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MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

ABSTRACT: This review summarizes the current knowledge linking cancer and neuro-degenerative diseases to dysregulation of microRNA network following pesticide exposure. Most findings revealed differential miRNA expression targeting biomolecules and pathways involved in various neoplastic localizations and neurodegenerative diseases. A growing body of evidence in recent literature indicates that alteration of specific miRNAs can represent an early biomarker of disease following exposure to chemical agents, including pesticides. Different miRNAs seem to regulate cell proliferation, apoptosis, migration, invasion, and metastasis via many biological pathways through modulation of the expression of target mRNAs. The evaluation of miRNA expression levels may be used to develop new non-invasive strategies for the prediction and prognosis of many diseases, including cancer. However, the application of miRNAs as diagnostic and therapeutic biomarkers in the clinical field is extremely challenging.

SUBMITTER: Costa C

PROVIDER: S-EPMC7322123 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

Costa Chiara C Teodoro Michele M Rugolo Carmela Alessandra CA Alibrando Carmela C Giambò Federica F Briguglio Giusi G Fenga Concettina C

Toxicology reports 20200521

This review summarizes the current knowledge linking cancer and neuro-degenerative diseases to dysregulation of microRNA network following pesticide exposure. Most findings revealed differential miRNA expression targeting biomolecules and pathways involved in various neoplastic localizations and neurodegenerative diseases. A growing body of evidence in recent literature indicates that alteration of specific miRNAs can represent an early biomarker of disease following exposure to chemical agents, ...[more]

PMID: 32612936

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Project description:BACKGROUND:Minimally invasive specific biomarkers of neurodegenerative diseases (NDs) would facilitate patient selection and disease progression monitoring. We describe the assessment of circulating brain-enriched microRNAs as potential biomarkers for Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). METHODS:In this case-control study, the plasma samples were collected from 250 research participants with a clinical diagnosis of AD, FTD, PD, and ALS, as well as from age- and sex-matched control subjects (n?=?50 for each group), recruited from 2003 to 2015 at the University of Pennsylvania Health System, including the Alzheimer's Disease Center, the Parkinson's Disease and Movement Disorders Center, the Frontotemporal Degeneration Center, and the Amyotrophic Lateral Sclerosis Clinic. Each group was randomly divided into training and confirmation sets of equal size. To evaluate the potential of circulating microRNAs enriched in specific brain regions affected by NDs and present in synapses as biomarkers of NDs, the levels of 37 brain-enriched and inflammation-associated microRNAs in the plasma of all participants were measured using individual qRT-PCR. A "microRNA pair" approach was used for data normalization. RESULTS:MicroRNA pairs and their combinations (classifiers) capable of differentiating NDs from control and from each other were defined using independently and jointly analyzed training and confirmation datasets. AD, PD, FTD, and ALS are differentiated from control with accuracy of 0.89, 0.90, 0.88, and 0.83 (AUCs, 0.96, 0.96, 0.94, and 0.93), respectively; NDs are differentiated from each other with accuracy ranging from 0.77 (AUC, 0.87) for AD vs. FTD to 0.93 (AUC, 0.98) for AD vs. ALS. The data further indicate sex dependence of some microRNA markers. The average increase in accuracy in distinguishing ND from control for all and male/female groups is 0.06; the largest increase is for ALS, from 0.83 for all participants to 0.92/0.98 for male/female participants. CONCLUSIONS:The work presented here suggests the possibility of developing microRNA-based diagnostics for detection and differentiation of NDs. Larger multicenter clinical studies are needed to further evaluate circulating brain-enriched microRNAs as biomarkers for NDs and to investigate their association with other ND biomarkers in clinical trial settings.

Project description:BackgroundAdult-onset neurodegenerative diseases affect millions and negatively impact health care systems worldwide. Evidence suggests that air pollution may contribute to aggravation of neurodegeneration, but studies have been limited.ObjectiveWe examined the potential association between long-term exposure to particulate matter ≤2.5μm in aerodynamic diameter [fine particulate matter (PM2.5)] and disease aggravation in Alzheimer's (AD) and Parkinson's (PD) diseases and amyotrophic lateral sclerosis (ALS), using first hospitalization as a surrogate of clinical aggravation.MethodsWe used data from the New York Department of Health Statewide Planning and Research Cooperative System (SPARCS 2000-2014) to construct annual county counts of first hospitalizations with a diagnosis of AD, PD, or ALS (total, urbanicity-, sex-, and age-stratified). We used annual PM2.5 concentrations estimated by a prediction model at a 1-km2 resolution, which we aggregated to population-weighted county averages to assign exposure to cases based on county of residence. We used outcome-specific mixed quasi-Poisson models with county-specific random intercepts to estimate rate ratios (RRs) for a 1-y PM2.5 exposure. We allowed for nonlinear exposure-outcome relationships using penalized splines and accounted for potential confounders.ResultsWe found a positive nonlinear PM2.5-PD association that plateaued above 11 μg/m3 (RR=1.09, 95% CI: 1.04, 1.14 for a PM2.5 increase from 8.1 to 10.4 μg/m3). We also found a linear PM2.5-ALS positive association (RR=1.05, 95% CI: 1.01, 1.09 per 1-μg/m3 PM2.5 increase), and suggestive evidence of an association with AD. We found effect modification by age for PD and ALS with a stronger positive association in patients <70 years of age but found insufficient evidence of effect modification by sex or urbanization level for any of the outcomes.ConclusionOur findings suggest that annual increase in county-level PM2.5 concentrations may contribute to clinical aggravation of PD and ALS. Importantly, the average annual PM2.5 concentration in our study was 8.1 μg/m3, below the current American national standards, suggesting the standards may not adequately protect the aging population. https://doi.org/10.1289/EHP7425.

Project description:Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics.

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MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

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MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

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