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1.
J Clin Pathol ; 73(9): 535-543, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32616540

RESUMO

Dilated cardiomyopathy (DCM) represents a common genetic cause of mechanical and/or electrical dysfunction leading to heart failure (HF) onset for which truncating variants in titin (TTN) gene result in the most frequent mutations. Moreover, myocyte and endothelial cell apoptosis is a key endophenotype underlying cardiac remodelling. Therefore, a deeper knowledge about molecular networks leading to acute injury and apoptosis may reveal novel circulating biomarkers useful to better discriminate HF phenotypes, patients at risk of heart transplant as well as graft reject in order to improve personalised therapy. Remarkably, increased plasma levels of cell-free DNA (cfDNA) may reflect the extent of cellular damage, whereas circulating mitochondrial DNA (mtDNA) may be a promising biomarker of poor prognosis in patients with HF. Furthermore, some panels of circulating miRNAs may improve the stratification of natural history of disease. For example, a combination of miR-558, miR-122* and miR-520d-5p, as well as miR-125a-5p, miR-550a-5p, miR-638 and miR-190a, may aid to discriminate different phenotypes of HF ranging from preserved to reduced ejection fraction. We give update on the most relevant genetic determinants involved in DCM and discuss the putative role of non-invasive biomarkers to overcome current limitations of the reductionist approach in HF management.


Assuntos
Apoptose/genética , Biomarcadores/análise , Cardiomiopatia Dilatada/complicações , MicroRNA Circulante/genética , Epigênese Genética , Insuficiência Cardíaca/genética , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Ácidos Nucleicos Livres , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Medicina de Precisão
2.
Analyst ; 145(12): 4173-4180, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32490854

RESUMO

Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.


Assuntos
MicroRNA Circulante/sangue , Corantes Fluorescentes/química , Análise Espectral Raman , Neoplasias da Bexiga Urinária/diagnóstico , Betacoronavirus/isolamento & purificação , Biomarcadores Tumorais/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Ouro/química , Humanos , Limite de Detecção , Microscopia Confocal , Nanoestruturas/química , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sistemas Automatizados de Assistência Junto ao Leito , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
3.
Int J Sports Med ; 41(9): 582-588, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32353882

RESUMO

Acute prolonged endurance running has been shown to alter muscle-specific circulating microRNA (miRNA) levels. Here, eighteen participants completed an 8 km run. We assessed the levels of hsa-miR-1-3p, -133a-3p, -133b, and -206 and their correlation with conventional biomarkers following exercise. Compared to before exercise (Pre), 8 km run significantly increased the lactate level immediately after exercise (0 h). Myoglobin (Mb) level increased at 0 h while creatine kinase (CK) level increased 24 h after exercise (24 h). The levels of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (cTnI) were all elevated at 24 h and within the normal physiological range; The levels of hsa-miR-1-3p, -133a-3p, -133b significantly increased at 0 h but only hsa-miR-133a-3p still elevated at 24 h. Only hsa-miR-206 level decreased at 24 h; Additionally, the changes of hsa-miR-1-3p and hsa-miR-133a-3p were correlated with Mb at 24 h. These findings suggest that muscle-specific miRNA elevation in plasma is likely physiological and that these miRNA may be used as potential biomarkers for load monitoring in individuals.


Assuntos
MicroRNA Circulante/sangue , Músculo Esquelético/metabolismo , Resistência Física/fisiologia , Corrida/fisiologia , Adaptação Fisiológica , Biomarcadores/sangue , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Masculino , Músculo Esquelético/lesões , Consumo de Oxigênio/fisiologia , Condicionamento Físico Humano/fisiologia , Mecânica Respiratória/fisiologia , Corrida/lesões , Adulto Jovem
4.
PLoS One ; 15(5): e0232411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392259

RESUMO

Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-ß/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.


Assuntos
MicroRNAs/genética , Lesões Experimentais por Radiação/genética , Pneumonite por Radiação/genética , Animais , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Feminino , Coração/efeitos da radiação , Humanos , Pulmão/metabolismo , Pulmão/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , MicroRNAs/sangue , MicroRNAs/metabolismo , Miocárdio/metabolismo , Modelos de Riscos Proporcionais , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/metabolismo , Pneumonite por Radiação/sangue , Pneumonite por Radiação/metabolismo , Especificidade da Espécie , Distribuição Tecidual
5.
Stroke ; 51(6): 1835-1843, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32397936

RESUMO

Background and Purpose- oxLDL (oxidized low-density lipoprotein) has been known for its potential to induce endothelial dysfunction and used as a major serological marker of oxidative stress. Recently, LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1), a lectin-like receptor for oxLDL, has attracted attention in studies of neuronal apoptosis and stroke. We aim to investigate the impact of LOX-1-deficiency on spontaneous hypertension-related brain damage in the present study. Methods- We generated a LOX-1 deficient strain on the genetic background of stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of severe hypertension and spontaneous stroke. In this new disease model with stroke-proneness, we monitored the occurrence of brain abnormalities with and without salt loading by multiple procedures including T2 weighted magnetic resonance imaging and also explored circulatory miRNAs as diagnostic biomarkers for cerebral ischemic injury by microarray analysis. Results- Both T2 weighted magnetic resonance imaging abnormalities and physiological parameter changes could be detected at significantly delayed timing in LOX-1 knockout rats compared with wild-type SHRSP, in either case of normal rat chow and salt loading (P<0.005 in all instances; n=11-20 for SHRSP and n=13-23 for LOX-1 knockout rats). There were no significant differences in the form of magnetic resonance imaging findings between the strains. A number of miRNAs expressed in the normal rat plasma, including rno-miR-150-5p and rno-miR-320-3p, showed significant changes after spontaneous brain damage in SHRSP, whereas the corresponding changes were modest or almost unnoticeable in LOX-1 knockout rats. There appeared to be the lessening of correlation of postischemic miRNA alterations between the injured brain tissue and plasma in LOX-1 knockout rats. Conclusions- Our data show that deficiency of LOX-1 has a protective effect on spontaneous brain damage in a newly generated LOX-1-deficient strain of SHRSP. Further, our analysis of miRNAs as biomarkers for ischemic brain damage supports a potential involvement of LOX-1 in blood brain barrier disruption after cerebral ischemia. Visual Overview- An online visual overview is available for this article.


Assuntos
Barreira Hematoencefálica , Isquemia Encefálica , Deleção de Genes , Hipertensão , Receptores Depuradores Classe E/deficiência , Acidente Vascular Cerebral , Animais , Barreira Hematoencefálica/lesões , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , MicroRNA Circulante , Hipertensão/sangue , Hipertensão/genética , Hipertensão/patologia , MicroRNAs/sangue , MicroRNAs/genética , Ratos , Ratos Endogâmicos SHR , Ratos Transgênicos , Receptores Depuradores Classe E/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia
6.
PLoS One ; 15(4): e0231040, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240265

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been linked to several diseases and to regulation of almost every biological process. This together with their stability while freely circulating in blood suggests that they could serve as minimal-invasive biomarkers for a wide range of diseases. Successful miRNA-based biomarker discovery in plasma is dependent on controlling sources of preanalytical variation, such as cellular contamination and hemolysis, as they can be major causes of altered miRNA expression levels. Analysis of plasma quality is therefore a crucial step for the best output when searching for novel miRNA biomarkers. METHODS: Plasma quality was assessed by three different methods in samples from mother-child duos (maternal and cord blood, N = 2x38), with collection and storage methods comparable to large cohort study biobanks. Total RNA was isolated and the expression profiles of 201 miRNAs was obtained by qPCR to identify differentially expressed miRNAs in cord and maternal plasma samples. RESULTS: All three methods for quality assurance indicate that the plasma samples used in this study are of high quality with very low levels of contamination, suitable for analysis of circulating miRNAs. We identified 19 significantly differentially expressed miRNAs between cord and maternal plasma samples (paired t-tests, FDR<0.05, and fold change>±1.5), and we observed low correlation of miRNA transcript levels between cord and maternal samples throughout our dataset. CONCLUSIONS: Our findings suggest that good quality plasma samples suitable for miRNA profiling can be achieved from samples collected and stored by large biobanks. Incorporation of extensive quality control measures, such as those established here, would be beneficial for future projects. The overall low correlation of miRNA expression between cord and maternal samples is an interesting observation, and promising for our future studies on identification of miRNA-based biomarkers in cord blood plasma, considering that these samples were collected at term and some exchange of blood components between cord and maternal blood frequently occur.


Assuntos
Biomarcadores/sangue , MicroRNA Circulante/genética , MicroRNA Circulante/metabolismo , Plasma/metabolismo , Bancos de Espécimes Biológicos , Criança , Saúde da Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Mães , Projetos Piloto
7.
PLoS One ; 15(4): e0231116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251457

RESUMO

BACKGROUND: MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS: Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high-grade dysplasia (HGD). RESULTS: Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION: Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.


Assuntos
Adenocarcinoma/diagnóstico , MicroRNA Circulante/genética , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Isoformas de RNA/genética , Adenocarcinoma/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Confiabilidade dos Dados , Neoplasias Esofágicas/sangue , Carcinoma de Células Escamosas do Esôfago/sangue , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Sensibilidade e Especificidade
8.
PLoS One ; 15(4): e0231402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271829

RESUMO

BACKGROUND: Turner syndrome (TS) is a chromosomal disorder, in which a female is partially or entirely missing one of the two X chromosomes, with a prevalence of 1:2500 live female births. The present study aims to identify a circulating microRNA (miRNA) signature for TS patients with and without congenital heart disease (CHD). METHODS: Microarray platform interrogating 2549 miRNAs were used to detect the miRNA abundance levels in the blood of 33 TS patients and 14 age-matched healthy volunteer controls (HVs). The differentially abundant miRNAs between the two groups were further validated by RT-qPCR. RESULTS: We identified 60 differentially abundant miRNA in the blood of TS patients compared to HVs, from which, 41 and 19 miRNAs showed a higher and a lower abundance levels in TS patients compared to HVs, respectively. RT-qPCR confirmed the significantly higher abundance levels of eight miRNAs namely miR-374b-5p, miR-199a-5p, miR-340-3p, miR-125b-5p, miR-30e-3p, miR-126-3p, miR-5695, and miR-26b-5p in TS patients as compared with the HVs. The abundance level of miR-5695 was higher in TS patients displaying CHD as compared to TS patients without CHD (p = 0.0265; log2-fold change 1.99); whereas, the abundance level of miR-126-3p was lower in TS patients with congenital aortic valve disease (AVD) compared to TS patients without BAV (p = 0.0139, log2-fold change 1.52). The clinical feature statistics revealed that miR-126-3p had a significant correlation with sinotubular junction Z-score (r = 0.42; p = 0.0154). CONCLUSION: The identified circulating miRNAs signature for TS patients with manifestations associated with cardiovascular diseases provide new insights into the molecular mechanism of TS that may guide the development of novel diagnostic approaches.


Assuntos
MicroRNA Circulante/sangue , Síndrome de Turner/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Cardiopatias/complicações , Cardiopatias/congênito , Cardiopatias/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Cariótipo , Síndrome de Turner/complicações , Síndrome de Turner/genética , Adulto Jovem
9.
PLoS One ; 15(4): e0231394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287312

RESUMO

miRNAs regulate post-transcriptional gene expression in metazoans, and thus are involved in many fundamental cellular biological processes. Extracellular miRNAs are also found in most human biofluids including plasma. These circulating miRNAs constitute a long distance inter cellular communication system and are potentially useful biomarkers. High throughput technologies like microarrays are able to scan a complete miRNome providing useful detection scores that are underexplored. We proposed to answer how many and which miRNAs are detectable in plasma or extracellular vesicles as these questions have not yet been answered. We set out to address this knowledge gap by analyzing the mirRNome in plasma and corresponding extracellular vesicles (EVs) from 12 children affected by retinoblastoma (Rb) a childhood intraocular malignant tumor, as well as from 12 healthy similarly aged controls. We calculated an average of 537 detectable miRNAs in plasma and 625 in EVs. The most miRNA enriched compartment were EVs from Rb cases with an average of 656 detectable elements. Using hierarchical clustering with the detection scores, we generated broad detection mirnome maps and identified a plasma signature of 19 miRNAs present in all Rb cases that is able to discriminate cases from controls. An additional 9 miRNAs were detected in all the samples; within this group, miRNA-5787 and miRNA-6732-5p were highly abundant and displayed very low variance across all the samples, suggesting both are good candidates to serve as plasma references or normalizers. Further exploration considering participant's sex, allowed discovering 5 miRNAs which corresponded only to females and 4 miRNAs corresponding only to males. Target and pathway analysis of these miRNAs revealed hormonal function including estrogen, thyroid signaling pathways and testosterone biosynthesis. This approach allows a comprehensive unbiased survey of a circulating miRNome landscape, creating the possibility to define normality in mirnomic profiles, and to locate where in these miRNome profiles promising and potentially useful circulating miRNA signatures can be found.


Assuntos
Vesículas Extracelulares/metabolismo , MicroRNAs/sangue , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Pré-Escolar , MicroRNA Circulante/sangue , Análise por Conglomerados , Análise Discriminante , Feminino , Humanos , Lactente , Masculino , MicroRNAs/análise , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Retina/genética , Retinoblastoma/genética
10.
PLoS One ; 15(4): e0232211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330203

RESUMO

BACKGROUND: Circulating microRNAs (miRNAs) have been shown to dysregulate in many cancer types including hepatocellular carcinoma (HCC). The purpose of this study was to examine the potential diagnostic or prognostic roles of circulating miRNAs in patients with hepatitis B virus (HBV)-related HCC. METHODS: Paired cancerous and adjacent non-cancerous liver tissue specimens of patients with HBV-related HCC were used as a discovery set for screening 800 miRNAs by a Nanostring quantitative assay. Differentially expressed miRNAs were then examined by SYBR green quantitative RT-PCR in a validation cohort of serum samples obtained from 70 patients with HBV-related HCC, 70 HBV patients without HCC and 50 healthy controls. RESULTS: The discovery set identified miR-223-3p, miR-199a-5p and miR-451a significantly lower expressed in cancerous tissues compared with non-cancerous tissues. In the validated cohort, circulating miR-223-3p levels were significantly lower in the HCC group compared with the other groups. The combined use of serum alpha-fetoprotein and miR-223-3p displayed high sensitivity for detecting early HCC (85%) and intermediate/advanced stage HCC (100%). Additionally, serum miR-223-3p had a negative correlation with tumor size and BCLC stage. On multivariate analysis, serum miR-223-3p was identified as an independent prognostic factor of overall survival in patients with HCC. In contrast, circulating miRNA-199a-5p and miR-451a did not show any clinical benefit for the diagnosis and prognostic prediction of HCC. CONCLUSIONS: Our results demonstrated that miR-223-3p was differentially expressed in cancerous compared with paired adjacent non-cancerous tissues. In addition, circulating miRNA-223-3p could represent a novel diagnostic and prognostic marker for patients with HBV-related HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , MicroRNA Circulante/genética , Hepatite B Crônica/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
World Neurosurg ; 138: 425-435, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251831

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive primary malignancy of the central nervous system. The standard used to monitor disease progression and therapeutic response has been magnetic resonance imaging, which is usually obtained preoperatively and postoperatively. Patients with GBM are monitored every 2-3 months and scans are repeated until progression is detected. Sometimes there is an inability to detect tumor progression or difficulty in differentiating tumor progression from pseudoprogression. With the difficulty of distinguishing disease progression, as well as the cost of imaging, there may be a need for the existence of a noninvasive liquid biopsy. There is no reliable biomarker for GBM that can be used for liquid biopsy, but if one could be detected in serum or cerebrospinal fluid and vary with tumor burden, then, it could be developed into one. MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that posttranscriptionally control gene expression. They play vital roles in tumor progression, migration, invasion, and stemness. Because miRNAs are secreted in stable forms in bodily fluid, either via extracellular vesicles or in cell-free form, they have great potential as biomarkers that can be used for liquid biopsy. Various miRNAs that are dysregulated in GBM have been identified in tissue, cerebrospinal fluid, and serum samples. There needs to be standardization of sample collection and quantification for both cell-free and exosomal-derived samples. Further studies need to be performed on larger cohorts to evaluate the sensitivity and specificity of not just miRNAs but most potential biomarkers.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , MicroRNA Circulante/biossíntese , Glioblastoma/diagnóstico , Glioblastoma/patologia , Biópsia Líquida/métodos , RNA Neoplásico/biossíntese , Neoplasias Encefálicas/cirurgia , MicroRNA Circulante/genética , Glioblastoma/cirurgia , Humanos , RNA Neoplásico/genética
12.
Medicine (Baltimore) ; 99(17): e19971, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332683

RESUMO

Coronary artery disease (CAD) is the second leading cause of death after stroke in China. Percutaneous coronary intervention (PCI) significantly improves the prognosis of CAD patients. This study aimed to evaluate the diagnostic value of circulating microRNAs (miRNAs) in patients with severe CAD requiring PCI. The plasma miRNA profiles were determined using miRNA microarray. The relative expression levels of differentially expressed miRNA were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Nine miRNAs (ebv-miR-BART12, ebv-miR-BART16, let-7i-5p, miR-130a-3p, miR-26a-5p, miR-3149, miR-3152-3p, miR-32-3p, and miR-149-3p) were differentially expressed between severe CAD and control groups. Four miRNAs (let-7i-5p, miR-32-3p, miR-3149, and miR-26a-5p) validated by qRT-PCR showed good diagnostic accuracy, with the area under the receiver operating characteristic curves (AUCs) of 0.634 (95% confidence interval [CI] 0.528-0.739), 0.745 (95%CI 0.649-0.84), 0.795 (95%CI 0.709-0.88), and 0.818 (95%CI 0.739-0.897), respectively. Furthermore, the combination of these 4 miRNAs exhibited better diagnostic performance compared with any individual miRNA, with an AUC of 0.837 (95%CI 0.763-0.911). These data indicate that plasma let-7i-5p, miR-32-3p, miR-3149, and miR-26a-5p have promising diagnostic value for severe CAD.


Assuntos
MicroRNA Circulante/análise , Doença da Artéria Coronariana/sangue , Área Sob a Curva , Biomarcadores/análise , Biomarcadores/sangue , China , MicroRNA Circulante/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Curva ROC
13.
Arch Biochem Biophys ; 684: 108331, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151564

RESUMO

BACKGROUND AND AIM: Osteoporosis is a systemic skeletal disorder that increases bone fragility and the risk of fractures. Recent studies have shown that miRNAs possess a pivotal role in osteoporosis development. This study aimed to evaluate the expression profiles of sera miRNA-208a-3p, miRNA-155-5p, and miRNA-637, to examine relation to osteoporosis and suggest the possible mechanisms of action to be used as innovative biomarkers for the diagnosis of osteoporosis among pre- and postmenopausal females. SUBJECT AND METHOD: In this pilot study, the blood samples were collected from 140 women who were divided depending on DEXA results (T-score) as following; osteoporotic patients with T-score ≤ -2.5 and healthy controls with T-score ≥ -1. Then, each group was subdivided into pre- and postmenopausal females (each, n = 35). The expression profiles of the studied miRNAs were measured using real-time polymerase chain reaction (RT-PCR). RESULTS: Serum miRNA-208a-3p was significantly upregulated, whereas miRNA-155-5p was markedly downregulated in the premenopausal patients compared to its respective controls. However, the miRNA-637 level showed a non-significant decrease in premenopausal patients than their controls. Moreover, the three studied miRNAs were significantly upregulated in the postmenopausal patients when compared to their respective controls, and premenopausal osteoporotic ones. CONCLUSION: Differential expression of these miRNAs suggests their association with osteoporosis pathogenesis and elucidate their promising roles in the diagnosis of osteoporosis.


Assuntos
MicroRNA Circulante/metabolismo , MicroRNAs/metabolismo , Osteoporose Pós-Menopausa/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Projetos Piloto , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Curva ROC , Estatísticas não Paramétricas
14.
Cancer Sci ; 111(6): 2104-2115, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215990

RESUMO

Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , MicroRNA Circulante/sangue , Vesículas Extracelulares , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade
15.
Arterioscler Thromb Vasc Biol ; 40(5): 1392-1399, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32160777

RESUMO

OBJECTIVE: Venous thrombosis (VT) is a complex condition with a highly heritable genetic component that predisposes one to its development. Certain microRNAs (miRNAs) might be used as biomarkers of VT, but few studies have examined miRNA expression in this respect. The aim of the present work was to identify a plasma miRNA profile associated with VT. Approach and Results: miRNAs were analyzed by quantitative polymerase chain reaction in plasma samples from members of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) population (n=935). A discovery phase involving the screening of 752 miRNAs from a subset of 104 GAIT-2 subjects was followed by an internal validation phase in which the selected miRNAs were quantified in the whole GAIT-2 population. In the discovery phase, 16 miRNAs were selected, including 9 associated with VT and 7 that correlated with an intermediate phenotype of VT. In the next phase, 4 miRNAs were validated as differentially expressed (false discovery rate, <0.1) in VT: hsa-miR-126-3p, hsa-miR-885-5p, hsa-miR-194-5p, and hsa-miR-192-5p. The 4 miRNAs each returned a significant (P<0.05) odds ratio for VT (range of 1.3-1.8). A risk model including the 4 miRNAs, age, and sex returned an area under the receiver operating characteristic curve of 0.77. Moreover, all 4 miRNAs showed significant correlations with intermediate phenotypes of VT (eg, protein S and factor VII). The targets of the miRNAs in the blood coagulation pathway and their interactions are also discussed. CONCLUSIONS: The present results suggest a 4-miRNA plasma profile associated with VT is of potential use in predicting the risk of this condition.


Assuntos
Coagulação Sanguínea/genética , MicroRNA Circulante/genética , Perfilação da Expressão Gênica/métodos , Reação em Cadeia da Polimerase , Transcriptoma , Trombose Venosa/genética , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Predisposição Genética para Doença , Hereditariedade , Humanos , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Espanha , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
16.
Life Sci ; 248: 117473, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114007

RESUMO

MicroRNAs (miRNAs) are a group of tiny molecules of 18-22 nucleotide long noncoding RNA that regulate the post-transcriptional gene expression through translational inhibition and/or mRNA destabilization. Because of their involvement in important developmental processes, it is highly likely that the altered expression of miRNAs could be associated with abnormal conditions like suboptimal growth or diseases. Thus, the expression of miRNAs can be used as biomarkers in pathophysiological conditions. Recently, a handful of miRNAs are detected in cell-free conditions including biofluids and cell culture media and they exhibit specific expression patterns that are associated with altered physiological conditions. Extracellular miRNAs are not only extremely stable outside cells in a variety of biofluids but also they are easy to acquire. These characteristics led to the idea of using extracellular miRNAs as a potential biomarker for the onset and prognosis of cancer. Although miRNAs have been proposed as a potential diagnostic tool for cancer detection, their application in the routine clinical investigation is yet to come. First, this review will provide an insight into the extracellular miRNAs, particularly, their release mechanisms and characteristics, and the potential of extracellular miRNAs as a biomarker in cancer detection. Finally, it will discuss the potential of using extracellular miRNAs in different cancer diagnoses and challenges associated with the clinical application of extracellular miRNAs as noninvasive biomarkers.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/diagnóstico , Neoplasias/genética , RNA Neoplásico/genética , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Detecção Precoce de Câncer/métodos , Exossomos/química , Feminino , Humanos , Masculino , Neoplasias/sangue , Neoplasias/patologia , Especificidade de Órgãos , Prognóstico , RNA Neoplásico/sangue
17.
Cancer Sci ; 111(5): 1711-1723, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32155300

RESUMO

Epstein-Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV-miR-BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV DNA were independent risk for shorter distant metastasis-free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44-5.97, P = .003; HR = 2.27, 95% CI, 1.26-4.10, P = .006) in multivariate Cox regression. Epstein-Barr virus DNA, miR-BART7-3p, and miR-BART13-3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR-BART7-3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89-9.01, P < .001; HR = 2.14, 95% CI, 1.04-4.42, P = .039). The 4-year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR-BART7-3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR-BART7-3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR-BART7-3p and EBV DNA after radiotherapy (P < .001). Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS.


Assuntos
MicroRNA Circulante/sangue , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , RNA Viral/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , DNA Viral/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Prognóstico , Análise de Sobrevida , Adulto Jovem
18.
Ir J Med Sci ; 189(3): 933-937, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32064546

RESUMO

BACKGROUND: Recent study reported that microRNA-142 (miR-142) were up-regulated in the atherosclerotic plaques, which may be responsible for pathogenesis of atherosclerosis. However, whether it associates with presence of acute myocardial infarction (AMI), and its prognostic value is still unknown. We, therefore, investigated the association between miR-142 expression and presence of AMI, and its prognostic value in AMI patients. METHODS: We included 300 AMI patients and 100 subjects as the control group. MiR-142 content was detected by quantitative real-time polymerase chain reaction. MiR-142 level was identified in all subjects. The multivariate logistic regression analysis were performed to evaluate the risk factors of AMI. The Kaplan-Meier analysis was performed to determine the major adverse cardiovascular and cerebrovascular events (MACCE)-free survival. RESULTS: AMI group had significantly higher miR-142 level in comparison to the controls [4.10 (2.03-7.43) vs. 1.92 (0.91-2.91), p < 0.001], moreover, miR-142 content was significantly associated with cardiac troponin I (cTnI) level (r = 0.707, p < 0.001). The MACCE-free survival was significantly lower over 24-month for patients in miR-142 high expression group (72.4% ± 5.6% vs. 76.4% ± 5.1%) (p = 0.022). After adjusting for the traditional risk factors, the odds ratios of miR-142 was 14.74 (95% CI, 2.15-101.24). The multivariate logistic regression analysis revealed that miR-142 level significantly associated with presence of AMI (p < 0.001). CONCLUSION: The serum level of miR-142 was increased in AMI patients when compared with health population. Furthermore, use of this marker may allow a certain predictor of the MACCE in AMI patients.


Assuntos
MicroRNA Circulante/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Prognóstico , Fatores de Risco , Análise de Sobrevida
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