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1.
Cardiol Rev ; 30(1): 16-23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32897886

RESUMO

Heart failure (HF) remains a major cause of death and disability worldwide. Currently, B-type natriuretic peptide and N-terminal probrain natriuretic peptide are diagnostic biomarkers used in HF. Although very sensitive, they are not specific enough and do not allow the prediction or early diagnosis of HF. Many ongoing studies focus on determining the underlying cause and understanding the mechanisms of HF on the cellular level. MicroRNAs (miRNAs) are noncoding RNAs, which control the majority of cellular processes and therefore are considered to have a potential clinical application in HF. In this review, we aim to provide synthesized information about miRNAs associated with ejection fraction, HF etiology, diagnosis, and prognosis, as well as outline therapeutic application of miRNAs in HF. Further, we discuss methodological challenges associated with the analysis of miRNAs and provide recommendations for defining a study population, collecting blood samples, and selecting detection methods to study miRNAs in a reliable and reproducible way. This review is intended to be an accessible tool for clinicians interested in the field of miRNAs and HF.


Assuntos
MicroRNA Circulante , Insuficiência Cardíaca , Biomarcadores/sangue , MicroRNA Circulante/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , MicroRNAs/uso terapêutico , Guias de Prática Clínica como Assunto
2.
Cells ; 10(12)2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34944012

RESUMO

The SARS-CoV-2 (COVID-19) pandemic has caused millions of deaths worldwide. Early risk assessment of COVID-19 cases can help direct early treatment measures that have been shown to improve the prognosis of severe cases. Currently, circulating miRNAs have not been evaluated as canonical COVID-19 biomarkers, and identifying biomarkers that have a causal relationship with COVID-19 is imperative. To bridge these gaps, we aim to examine the causal effects of miRNAs on COVID-19 severity in this study using two-sample Mendelian randomization approaches. Multiple studies with available GWAS summary statistics data were retrieved. Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated. This study provides a novel way of utilizing miRNA eQTL data to help us identify potential miRNA biomarkers to make better and early diagnoses and risk assessments of severe COVID-19 cases.


Assuntos
COVID-19/genética , MicroRNA Circulante/genética , MicroRNAs/genética , Gravidade do Paciente , SARS-CoV-2/genética , Biomarcadores/sangue , COVID-19/sangue , MicroRNA Circulante/sangue , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , MicroRNAs/sangue , SARS-CoV-2/metabolismo
3.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641523

RESUMO

MicroRNAs, which circulate in blood, are characterized by high diagnostic value; in biomedical research, they can be considered as candidate markers of various diseases. Mature microRNAs of glial cells and neurons can cross the blood-brain barrier and can be detected in the serum of patients with autism spectrum disorders (ASD) as components of macrovesicles, macromolecular protein and low-density lipoprotein particles. In our present study, we have proposed an approach, in which microRNAs in protein complexes can be concentrated on the surface of AFM chips with oligonucleotide molecular probes, specific against the target microRNAs. MicroRNAs, associated with the development of ASD in children, were selected as targets. The chips with immobilized molecular probes were incubated in serum samples of ASD patients and healthy volunteers. By atomic force microscopy (AFM), objects on the AFM chip surface have been revealed after incubation in the serum samples. The height of these objects amounted to 10 nm and 6 nm in the case of samples of ASD patients and healthy volunteers, respectively. MALDI-TOF-MS analysis of protein components on the chip surface allowed us to identify several cell proteins. These proteins are involved in the binding of nucleic acids (GBG10, RT24, RALYL), in the organization of proteasomes and nucleosomes (PSA4, NP1L4), and participate in the functioning of the channel of active potassium transport (KCNE5, KCNV2).


Assuntos
Transtorno do Espectro Autista/sangue , Proteínas Sanguíneas/genética , MicroRNA Circulante/sangue , Microscopia de Força Atômica/instrumentação , Adulto , Proteínas Sanguíneas/metabolismo , Criança , MicroRNA Circulante/metabolismo , Feminino , Humanos , Masculino , Microscopia de Força Atômica/métodos , Pessoa de Meia-Idade , Canais de Potássio de Abertura Dependente da Tensão da Membrana/sangue , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
4.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638684

RESUMO

Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow's adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3' untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of "harmful" exosomes from obesity adipose tissues causes placental dysplasia during gestation.


Assuntos
Proteínas Semelhantes a Angiopoietina/metabolismo , MicroRNA Circulante/sangue , Células Endoteliais/metabolismo , Exossomos/metabolismo , Neovascularização Fisiológica , Obesidade Materna/sangue , Animais , Feminino , Humanos , Gravidez , Suínos
5.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638717

RESUMO

MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.


Assuntos
Fibrilação Atrial/sangue , Sinalização do Cálcio , Comunicação Celular , MicroRNA Circulante/sangue , Insuficiência Cardíaca/sangue , MicroRNAs/sangue , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/etiologia , Linhagem Celular , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino
6.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638993

RESUMO

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Defects in trophoblast invasion, differentiation of extravillous trophoblasts and spiral artery remodeling are key factors in PE development. Currently there are no predictive biomarkers clinically available for PE. Recent technological advancements empowered transcriptome exploration and led to the discovery of numerous non-coding RNA species of which microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most investigated. They are implicated in the regulation of numerous cellular functions, and as such are being extensively explored as potential biomarkers for various diseases. Altered expression of numerous lncRNAs and miRNAs in placenta has been related to pathophysiological processes that occur in preeclampsia. In the following text we offer summary of the latest knowledge of the molecular mechanism by which lnRNAs and miRNAs (focusing on the chromosome 19 miRNA cluster (C19MC)) contribute to pathophysiology of PE development and their potential utility as biomarkers of PE, with special focus on sample selection and techniques for the quantification of lncRNAs and miRNAs in maternal circulation.


Assuntos
MicroRNA Circulante/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , RNA Longo não Codificante/sangue , Biomarcadores/sangue , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 19/metabolismo , MicroRNA Circulante/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Gravidez , RNA Longo não Codificante/genética , Transcriptoma , Trofoblastos/metabolismo
7.
Glob Heart ; 16(1): 56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692380

RESUMO

Background: Sarcopenia is a critical finding in patients with chronic heart failure (CHF). However, the search for a definitive biomarker to predict muscle and functional decline in CHF remains elusive. Objectives: We aimed to correlate the circulating levels of selected miRs with the indexes of sarcopenia during healthy aging and in patients with CHF. Methods: We analyzed the association of circulating microRNAs (miRs) levels including miR-21, miR-434-3p, miR424-5p, miR-133a, miR-455-3p and miR-181a with sarcopenia indexes in male, 61-73 years old healthy controls and patients with CHF (N = 89-92/group). Results: Patients with CHF had lower hand-grip strength (HGS), appendicular skeletal mass index (ASMI) and physical capacity than healthy controls. Circulating miR-21 levels were higher and miR-181a, miR-133a, miR-434-3p and miR-455-3p levels were lower in patients with CHF than healthy controls. Among the sarcopenia indexes, HGS showed the strongest correlation with miR-133a while ASMI showed the strongest correlations with miR-133a, miR-434-3p and miR-455-3p. Among the miRs, miR-434-3p showed the highest area under the curve in testing for sensitivity and specificity for CHF. These changes were associated with higher expressions of the markers of inflammation, oxidative stress and muscle damage in CHF patients. Conclusion: Taken together, our data show that circulating miRs can be useful markers of muscle health and physical capacity in the sarcopenic elderly with CHF.


Assuntos
MicroRNA Circulante , Insuficiência Cardíaca , MicroRNAs , Sarcopenia , Idoso , Biomarcadores , MicroRNA Circulante/genética , Insuficiência Cardíaca/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/genética
8.
PLoS One ; 16(9): e0257805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570814

RESUMO

BACKGROUND: Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. METHODS: In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. RESULTS: The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. CONCLUSION: Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.


Assuntos
MicroRNA Circulante/sangue , Leptospirose/complicações , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Leptospirose/sangue , Leptospirose/genética , Hepatopatias/genética , Masculino , Redes e Vias Metabólicas , MicroRNAs/sangue , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida
9.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502360

RESUMO

Type 2 diabetes (T2D) represents one of the major health issues of this century. Despite the availability of an increasing number of anti-hyperglycemic drugs, a significant proportion of patients are inadequately controlled, thus highlighting the need for novel biomarkers to guide treatment selection. MicroRNAs (miRNAs) are small non-coding RNAs, proposed as useful diagnostic/prognostic markers. The aim of our study was to identify a miRNA signature occurring in responders to glucagon-like peptide 1 receptor agonists (GLP1-RA) therapy. We investigated the expression profile of eight T2D-associated circulating miRNAs in 26 prospectively evaluated diabetic patients in whom GLP1-RA was added to metformin. As expected, GLP1-RA treatment induced significant reductions of HbA1c and body weight, both after 6 and 12 months of therapy. Of note, baseline expression levels of the selected miRNAs revealed two distinct patient clusters: "high expressing" and "low expressing". Interestingly, a significantly higher percentage of patients in the high expression group reached the glycemic target after 12 months of treatment. Our findings suggest that the evaluation of miRNA expression could be used to predict the likelihood of an early treatment response to GLP1-RA and to select patients in whom to start such treatment, paving the way to a personalized medicine approach.


Assuntos
MicroRNA Circulante/análise , MicroRNA Circulante/genética , Diabetes Mellitus Tipo 2/genética , Adulto , Biomarcadores Farmacológicos/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Glucose/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Projetos Piloto , Transcriptoma/genética
10.
Sci Rep ; 11(1): 15815, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349188

RESUMO

Piedmontese cattle is known for double-muscle phenotype. MicroRNAs (miRNAs) play important role as regulators in skeletal muscle physiological processes, and we hypothesize that plasma miRNAs expression profiles could be affected by skeletal muscle growth status related to age. Plasma samples of cattle were collected during four different ages from first week of life until the time of commercial end of the fattening period before slaughter. Small-RNA sequencing data analysis revealed the presence of 40% of muscle-related miRNAs among the top 25 highly expressed miRNAs and, 19 miRNAs showed differential expression too. Using qRT-PCR, we validated in a larger bovine population, miRNAs involved in skeletal muscle physiology pathways. Comparing new-born with the other age groups, miR-10b, miR-126-5p, miR-143 and miR-146b were significantly up-regulated, whereas miR-21-5p, miR-221, miR-223 and miR-30b-5p were significantly down-regulated. High expression levels of miR-23a in all the groups were found. Myostatin, a negative regulator of skeletal muscle hypertrophy, was predicted as the target gene for miR-23a and miR-126-5p and we demonstrated their direct binding. Correlation analysis revealed association between miRNAs expression profiles and animals' weights along the age. Circulating miRNAs could be promising for future studies on their biomarker potentialities to beef cattle selection.


Assuntos
Biomarcadores/análise , MicroRNA Circulante/genética , Hipertrofia/diagnóstico , Músculo Esquelético/metabolismo , Doenças Musculares/diagnóstico , Miostatina/metabolismo , Fatores Etários , Animais , Peso Corporal , Bovinos , MicroRNA Circulante/análise , Hipertrofia/sangue , Hipertrofia/genética , Doenças Musculares/sangue , Doenças Musculares/genética , Miostatina/genética , Projetos Piloto
11.
Infect Genet Evol ; 94: 105020, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34343725

RESUMO

Nowadays, the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major global health problem. Intensive efforts are being employed to better understand this pathology and develop strategies enabling its early diagnosis and efficient treatment. In this study, we compared the signature of circulating miRNAs in plasma of COVID-19 patients versus healthy donors. MiRCURY LNA miRNA miRNome qPCR Panels were performed for miRNA signature characterization. Individual quantitative real-time PCR (qRT-PCR) was carried out to validate miRNome qPCR results. Receiver-operator characteristic (ROC) curve analysis was applied to assess the diagnostic accuracy of the most significantly deregulated miRNA(s) as potential diagnostic biomarker(s). Eight miRNAs were identified to be differentially expressed with miR-17-5p and miR-142-5p being down-regulated whilst miR-15a-5p, miR-19a-3p, miR-19b-3p, miR-23a-3p, miR-92a-3p and miR-320a being up-regulated in SARS-CoV-2-infected patients. ROC curve analyses revealed an AUC (Areas Under the ROC Curve) of 0.815 (P = 0.031), 0.875 (P = 0.012), and 0.850 (P = 0.025) for miR-19a-3p, miR-19b-3p, and miR-92a-3p, respectively. Combined ROC analyses using these 3 miRNAs showed a greater AUC of 0.917 (P = 0.0001) indicating a robust diagnostic value of these 3 miRNAs. These results suggest that plasma miR-19a-3p, miR-19b-3p, and miR-92a-3p expression levels could serve as potential diagnostic biomarker and/or a putative therapeutic target during SARS-CoV-2-infection.


Assuntos
COVID-19/sangue , MicroRNA Circulante/sangue , Adulto , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/fisiopatologia , MicroRNA Circulante/genética , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
12.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360904

RESUMO

Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called "exosomes" have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.


Assuntos
MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Cirrose Hepática/sangue , Cirrose Hepática/genética , Animais , Biomarcadores/sangue , Colangite Esclerosante/sangue , Colangite Esclerosante/complicações , Epigênese Genética , Exossomos/metabolismo , Fígado Gorduroso Alcoólico/sangue , Fígado Gorduroso Alcoólico/complicações , Regulação da Expressão Gênica , Hepatite Autoimune/sangue , Hepatite Autoimune/complicações , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/complicações , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações
13.
Biomed Res Int ; 2021: 6676107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368354

RESUMO

The present study is aimed at profiling circulating exosome-derived microRNAs (miRNAs/miRs) from patients with dermatomyositis (DM), in particular those complicated with interstitial lung disease (ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive. Fifteen participants were enrolled, including five patients with DM complicated with ILDs prior to treatment with circulating anti-MDA5 antibody-positive status [DM-ILD-MDA5 Ab(+)], five DM patients without ILDs who were negative for 16 detectable myositis-specific antibodies [DM-nonILD-MSA16(-)], and five age- and gender-matched healthy donor controls (HCs). The characteristics of the exosomes extracted by Ribo™ Exosome Isolation Reagent were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Differentially expressed miRNAs, determined by next-generation deep sequencing, were identified through the criteria of ∣log2 fold change | ≥1 and P < 0.01. A total of 38 miRNAs were significantly upregulated in exosomes from patients with DM-ILD-MDA5 Ab(+) compared to those from HC, while 21 miRNAs were significantly downregulated. Compared to exosomes derived from patients with DM-nonILD-MSA16(-), 51 miRNAs were significantly upregulated and 33 miRNAs were significantly downregulated from patients with DM-ILD-MDA5 Ab(+). A total of 73 exosomal miRNAs were significantly differentially expressed between DM-nonILD-MSA16(-) and HC. In particular, two miRNAs, Homo sapiens- (hsa-) miR-4488 and hsa-miR-1228-5p, were common differentially expressed miRNAs among three comparisons. GO and KEGG analyses suggested that several pathways may contribute the pathogenesis of DM-ILD-MDA5 Ab(+) and DM-nonILD-MSA16(-), while PPI network analysis of hsa-miR-4488 and hsa-miR-1228-5p indicated that their predicted target genes, DExD-box helicase 39B and MDM2, may be involved in the mechanisms of DM-ILD-MDA5 Ab(+).


Assuntos
Anticorpos/metabolismo , Dermatomiosite/sangue , Exossomos/genética , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/sangue , MicroRNAs/sangue , Adulto , Biomarcadores/sangue , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Dermatomiosite/complicações , Dermatomiosite/genética , Exossomos/ultraestrutura , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
Signal Transduct Target Ther ; 6(1): 300, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381015

RESUMO

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks' continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.


Assuntos
COVID-19/genética , Diabetes Mellitus/genética , MicroRNAs/genética , Glicoproteína da Espícula de Coronavírus/genética , Adulto , Fatores Etários , Idoso , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , China , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Exercício Físico , Exossomos/genética , Exossomos/metabolismo , Exossomos/virologia , Feminino , Regulação da Expressão Gênica , Células HEK293 , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Replicação Viral
15.
Environ Sci Pollut Res Int ; 28(39): 54282-54298, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34402004

RESUMO

Exposure to polycyclic aromatic hydrocarbons (PAHs) produced from various pyrogenic and petrogenic sources in the environment has been linked to a variety of toxic effects in the human body. Genome-wide analyses have shown that microRNAs (miRNAs) can function as novel and minimally invasive biomarkers of environmental exposure to PAHs. The objective of this study is to explore miRNA signatures associated with early health effects in response to chronic environmental exposure to PAHs. We systematically searched Scopus and PubMed databases for studies related to exposure of PAHs with changes in miRNA expression patterns that represent early health effects in the exposed population. Based on previous studies, we included 15 cell-based and 9 each of animal model and human population-based studies for assessment. A total of 11 differentially expressed PAH-responsive miRNAs were observed each in two or more cell-based studies (miR-181a and miR-30c-1), animal model studies (miR-291a and miR-292), and human population-based studies (miR-126, miR-142-5p, miR-150-5p, miR-24-3p, miR-27a-3p, miR-28-5p, and miR-320b). In addition, miRNAs belonging to family miR-122, miR-199, miR-203, miR-21, miR-26, miR-29, and miR-92 were found to be PAH-responsive in both animal model and cell-based studies; let-7, miR-126, miR-146, miR-30, and miR-320 in both cell-based and human population-based studies; and miR-142, miR-150, and miR-27 were found differentially expressed in both animal model and human population-based studies. The only miRNA whose expression was found to be altered in all the three groups of studies is miR-34c. Association of environmental exposure to PAHs with altered expression of specific miRNAs indicates that selective miRNAs can be used as early warning biomarkers in PAH-exposed population.


Assuntos
MicroRNA Circulante , MicroRNAs , Hidrocarbonetos Policíclicos Aromáticos , Biomarcadores , Exposição Ambiental , Estudo de Associação Genômica Ampla , Humanos , MicroRNAs/genética , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
16.
Curr Issues Mol Biol ; 43(2): 900-916, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34449536

RESUMO

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial-mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.


Assuntos
MicroRNA Circulante/sangue , Endometriose/sangue , Inflamação/patologia , Biomarcadores/sangue , MicroRNA Circulante/genética , Endometriose/diagnóstico , Endometriose/genética , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Fatores de Risco , Útero/metabolismo , Útero/patologia
17.
Cells ; 10(8)2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34440757

RESUMO

Circulating microRNAs (miRNAs) are key regulators of the crosstalk between tumor cells and immune response. In the present study, miRNAs (let-7c, miR-26a, miR-30d, miR-98, miR-195, miR-202) reported to be involved in the polarization of macrophages were examined for associations with the outcomes of non-small cell lung cancer (NSCLC) patients (N = 125) treated with first-line platinum-based chemotherapy. RT-qPCR was used to analyze miRNA expression levels in the plasma of patients prior to treatment. In our results, disease progression was correlated with high miR-202 expression (HR: 2.335; p = 0.040). Additionally, high miR-202 expression was characterized as an independent prognostic factor for shorter progression-free survival (PFS, HR: 1.564; p = 0.021) and overall survival (OS, HR: 1.558; p = 0.024). Moreover, high miR-202 independently predicted shorter OS (HR: 1.989; p = 0.008) in the non-squamous (non-SqCC) subgroup, and high miR-26a was correlated with shorter OS in the squamous (SqCC) subgroup (10.07 vs. 13.53 months, p = 0.033). The results of the present study propose that the expression levels of circulating miRNAs involved in macrophage polarization are correlated with survival measures in NSCLC patients, and their role as potential biomarkers merits further investigation.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , MicroRNA Circulante/sangue , Neoplasias Pulmonares/sangue , Ativação de Macrófagos , Macrófagos Associados a Tumor/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo , Microambiente Tumoral , Macrófagos Associados a Tumor/imunologia
18.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445710

RESUMO

Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the "gold standard" for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia.


Assuntos
Caquexia/diagnóstico , Caquexia/genética , MicroRNAs/genética , Tecido Adiposo/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , MicroRNA Circulante/análise , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Metabolismo Energético/fisiologia , Humanos , Inflamação/patologia , Biópsia Líquida/métodos , MicroRNAs/análise , MicroRNAs/sangue , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Neoplasias/complicações , Neoplasias/genética , Transdução de Sinais/genética , Perda de Peso/genética
19.
Am J Vet Res ; 82(8): 659-666, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34296940

RESUMO

OBJECTIVE: To identify differential microRNA (miRNA) expression in dogs with splenic hemangiosarcoma, splenic hematoma, and histologically normal spleens. ANIMALS: Dogs with splenic hemangiosarcoma (n = 10), splenic hematoma (n = 5), and histologically normal spleens (n = 5). PROCEDURES: Splenic tissue and serum samples were collected from dogs with splenic masses (ie, hemangiosarcoma or hematoma samples) and healthy control dogs (ie, control samples), and total RNA was extracted. Reverse transcription quantitative real-time PCR was performed with 28 miRNAs associated with hemangiosarcoma, angiosarcoma, or associated genes. Differential expression analysis was performed. RESULTS: Control tissue and serum samples had similar miRNA expression patterns, and hemangiosarcoma tissue and serum samples did not. Hemangiosarcoma serum samples had higher expression than hemangiosarcoma tissue for 13 miRNAs and lower expression for 1 miRNA. Control tissue and hemangiosarcoma tissue had varying expressions for 12 miRNAs, with 10 more highly expressed in control samples and 2 more highly expressed in hemangiosarcoma samples. Five miRNAs (miR-214-3p, miR-452, miR-494-3p, miR-497-5p, miR-543) had significantly different expression in serum between dogs with splenic masses (ie, hemangiosarcoma or hematoma) and serum of dogs with histologically normal spleens, with higher expression in the serum of dogs with splenic masses for all 5 miRNAs. CONCLUSIONS AND CLINICAL RELEVANCE: 5 circulating miRNAs were identified that distinguished dogs with splenic hemangiosarcoma or hematoma from those with histologically normal spleens. These 5 miRNAs had higher expression in dogs with splenic masses, indicating upregulation of these circulating miRNAs occurs in these splenic disease states. These miRNAs may be useful as a noninvasive screening tool that uses serum to identify dogs with splenic masses.


Assuntos
MicroRNA Circulante , Doenças do Cão , Hemangiossarcoma , MicroRNAs , Neoplasias Esplênicas , Animais , Doenças do Cão/genética , Cães , Hemangiossarcoma/genética , Hemangiossarcoma/veterinária , MicroRNAs/genética , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/veterinária
20.
Cancer Sci ; 112(10): 3995-4004, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34310776

RESUMO

Multiple myeloma (MM) is a refractory plasma cell tumor. In myeloma cells, the transcription factor IRF4, the master regulator of plasma cells, is aberrantly upregulated and plays an essential role in oncogenesis. IRF4 forms a positive feedback loop with MYC, leading to additional tumorigenic properties. In recent years, molecular targeted therapies have contributed to a significant improvement in the prognosis of MM. Nevertheless, almost all patients experience disease progression, which is thought to be a result of treatment resistance induced by various elements of the bone marrow microenvironment. Among these, the hypoxic response, one of the key processes for cellular homeostasis, induces hypoxia-adapted traits such as undifferentiation, altered metabolism, and dissemination, leading to drug resistance. These inductions are caused by ectopic gene expression changes mediated by the activation of hypoxia-inducible factors (HIFs). By contrast, the expression levels of IRF4 and MYC are markedly reduced by hypoxic stress. Notably, an anti-apoptotic capability is usually acquired under both normoxic and hypoxic conditions, but the mechanism is distinct. This fact strongly suggests that myeloma cells may survive by switching their dependent regulatory factors from IRF4 and MYC (normoxic bone marrow region) to HIF (hypoxic bone marrow microenvironment). Therefore, to achieve deep remission, combination therapeutic agents, which are complementarily effective against both IRF4-MYC-dominant and HIF-dominated fractions, may become an important therapeutic strategy for MM.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fatores Reguladores de Interferon/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Hipóxia Tumoral/fisiologia , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células da Medula Óssea/fisiologia , Desdiferenciação Celular , Hipóxia Celular/fisiologia , Movimento Celular/fisiologia , Microambiente Celular/fisiologia , MicroRNA Circulante/metabolismo , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/fisiologia , Retroalimentação Fisiológica , Glicólise/fisiologia , Hexoquinase/metabolismo , Homeostase , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores Imunológicos/uso terapêutico , Fatores Reguladores de Interferon/genética , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Terapia de Alvo Molecular/métodos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/fisiologia , Oxigênio , Pressão Parcial , Inibidores de Proteassoma/uso terapêutico , Proteínas Proto-Oncogênicas c-myc/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/antagonistas & inibidores , Regulação para Cima
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