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1.
Cancer Sci ; 110(12): 3718-3726, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31599471

RESUMO

Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.


Assuntos
MicroRNA Circulante/análise , Leiomiossarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Biomarcadores Tumorais/sangue , Análise por Conglomerados , Feminino , Humanos , Leiomiossarcoma/sangue , Neoplasias Uterinas/sangue
2.
Medicine (Baltimore) ; 98(39): e17297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574853

RESUMO

As a modifiable risk factor for cardiovascular disease, presence of hypertension (HT) necessitates the awareness of asymptomatic organ damage (AOD). The aim of this study was to measure plasma micro RNA-21 (miR-21) and the parameters that reflect AOD such as carotid intima-media thickness (CIMT), microalbuminuria (MAU) in hypertensive patients compared with healthy controls. In addition, the aim of this study was to evaluate plasma miR-21 levels in HT patients with AOD.This study was designed as a cross-sectional observational study. The study includes 2 groups: 32 patients with HT and 32 healthy controls. First, we compared these 2 groups. Then, to underline the relationship between plasma miR-21 and HT, hypertensive patients were divided into 2 groups: with AOD and without AOD.Sixteen patients with HT had AOD. MiR-21 levels significantly correlated with clinical systolic and diastolic blood pressure, MAU, C-reactive protein, and CIMT. CIMT, miR-21, and MAU levels were significantly higher in patients with AOD.Our study showed increased miR-21 levels in HT patients with AOD.


Assuntos
Albuminúria , Doenças Cardiovasculares , Hipertensão , MicroRNAs/sangue , Adulto , Albuminúria/diagnóstico , Albuminúria/etiologia , Doenças Assintomáticas/epidemiologia , Pressão Sanguínea/fisiologia , Proteína C-Reativa/análise , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Espessura Intima-Media Carotídea , MicroRNA Circulante/análise , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Turquia/epidemiologia
3.
Int J Cancer ; 144(9): 2169-2180, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30381824

RESUMO

Because of the different forms of circulating miRNAs in plasma, Argonaute2 (Ago2)-miRNAs and extracellular vesicles (EV-miRNAs), we examined the two forms of extracellular miRNAs in vitro and developed a unique methodology to detect circulating Ago2-miRNAs in small volumes of plasma. We demonstrated that Ago2-miR-21 could be released into the extracellular fluid by active export from viable cancer cells and cytolysis in vitro. As miR-21 and miR-200c were abundantly expressed in both metastatic liver sites and primary lesions, we evaluated Ago2-miR-21 as a candidate biomarker of both active export and cytolysis while Ago2-miR-200c as a biomarker of cytolysis in plasma obtained from colorectal cancer (CRC) patients before treatment and in a series of plasma obtained from CRC patients with liver metastasis who received systemic chemotherapy. The measurement of Ago2-miR-21 allowed us to distinguish CRC patients from subjects without CRC. The trend in ΔCt values for Ago2-miR-21 and -200c during chemotherapy could predict tumor response to ongoing treatment. Thus, capturing circulating Ago2-miRNAs from active export can screen patients with tumor burdens, while capturing them from passive release by cytolysis can monitor tumor dynamics during chemotherapy treatment.


Assuntos
Proteínas Argonauta/sangue , MicroRNA Circulante/análise , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , MicroRNA Circulante/metabolismo , Neoplasias Colorretais/patologia , Vesículas Extracelulares/patologia , Células HT29 , Humanos
4.
Transplantation ; 103(2): 329-335, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30444806

RESUMO

BACKGROUND: Delayed graft function (DGF), a common complication after transplantation of deceased donor kidneys, affects both short- and long-term outcomes. Currently available biomarkers during graft preservation lack sensitivity in predicting risk for DGF. The aim of this study is to identify cell-free micro ribonucleic acid (miRNA) biomarkers in graft preservation fluid predictive of DGF after kidney transplantation. METHODS: Vascular bed preservation fluid was collected from 48 kidney grafts from donation after circulatory death (DCD) or donation after brain death (DBD) donors. miRNA profiles were determined by polymerase chain reaction (PCR) array (n = 8) and validated by reverse transcription and quantitative PCR (n = 40). Graft function posttransplantation was defined as immediate good function (IF) or DGF. RESULTS: A total of 223 miRNAs fulfilled the preset parameters (Ct < 40 in 3 or more samples) and were included in the analysis. Thirty-two miRNAs were significantly different between DGF and IF kidney grafts (P < 0.05) but, after correction for multiple testing, only miR-505-3p remained significant. The significant association of high miR-505-3p levels with DGF was confirmed in an independent validation cohort using conventional reverse transcription and quantitative PCR detection. Multivariate analyses showed miR-505-3p as an independent predictor for DGF (odds ratio, 1.12; P = 0.028). If stratified for donor type, miR-505-3p levels remained significantly different between IF and DGF in DCD grafts (P < 0.01), but not in DBD grafts. Receiver operating characteristic curve analysis showed a high sensitivity and specificity (area under the curve, 0.833). CONCLUSIONS: In DCD grafts, high levels of miR-505-3p in preservation fluid are associated with increased risk of DGF after kidney transplantation. Further study is required to confirm the utility of cell-free miR-505-3p as prognostic biomarker for DGF.


Assuntos
MicroRNA Circulante/análise , Função Retardada do Enxerto/etiologia , Transplante de Rim/efeitos adversos , MicroRNAs/análise , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
5.
Microrna ; 7(3): 195-203, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29984665

RESUMO

BACKGROUND: MicroRNAs (miRNA) are expected as useful biomarkers for various diseases. We studied the pre-analytical factors causing variation in the analysis of miRNA. MATERIAL AND METHODS: Blood samples were collected from 25 healthy subjects. Plasma and serum were obtained from the same samples. The levels of miR-451, -16, -126, and -223 were analyzed using RT-qPCR. Cel-miR-39 was added as a spiked-in control in each sample. RESULTS: With the exception of miR-451, the levels of the miRNAs in plasma were higher than in serum. After high-speed centrifugation, the levels of miRNAs were almost equal between plasma and serum except for miR-451. Membrane filtration with 0.45 µm pore size reduced the levels of plasma miRNAs. The coagulation accelerators for serum processing did not affect the analysis of miRNA. The use of fraction containing particles of > 0.45 µm in size showed the inhibitory effect on the analysis of plasma miR-451. The RNase inhibitor was effective for protecting against the degradation of miRNAs. CONCLUSION: Plasma contains factors modifying miRNA profiles. The immediate processing of plasma with membrane filtration and RNase inhibitor may be a relevant method for achieving the stable analysis of miRNA.


Assuntos
Biomarcadores/análise , Coleta de Amostras Sanguíneas/normas , MicroRNA Circulante/análise , MicroRNA Circulante/genética , Plasma/química , Soro/química , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Plasma/metabolismo , Controle de Qualidade , Soro/metabolismo , Adulto Jovem
6.
Cancer Sci ; 109(9): 2897-2906, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29981251

RESUMO

Serum circulating microRNAs (c-miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one-step branched rolling circle amplification (BRCA) method to measure serum c-miRNAs levels for early diagnosis of breast cancer. Four c-miRNAs, c-miRNA16 (c-miR-16), c-miRNA21 (c-miR-21), c-miRNA155 (c-miR-155), and c-miRNA195 (c-miR-195) were isolated from the serum of 49 breast cancer patients and 19 healthy controls. Among them, 45 breast cancer patients and 15 healthy controls were analyzed using one-step BRCA, 4 breast cancer patients and 4 healthy controls were analyzed by quantitative real-time PCR assay [corrected]. The serum levels of c-miR16, c-miR21, c-miR155, and c-miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER-2 over-expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c-miR16, c-miR21, c-miR155, and c-miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c-miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real-time PCR (qRT-PCR) method show that the serum levels of c-miR16, c-miR21, c-miR155, and c-miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes.


Assuntos
Neoplasias da Mama/diagnóstico , MicroRNA Circulante/análise , Detecção Precoce de Câncer/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Adulto , Neoplasias da Mama/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
7.
Biochim Biophys Acta Rev Cancer ; 1870(2): 274-282, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29852194

RESUMO

Emerging evidence has demonstrated the feasibility of circulating miRNAs as robust non-invasive biomarkers for the diagnosis in colorectal cancer. The use of circulating miRNAs for the early detection of colorectal cancer (CRC) is of particular interest as it can offer a potential complementary approach to screening colonoscopy. However, the development of circulating miRNAs as "liquid biopsy" biomarkers for development into clinical screening tests has been hampered by several issues. In this article, we summarize the status of this field for the clinical utilization of miRNA biomarkers as liquid biopsies in colorectal cancer (CRC) and discuss their applications as screening tests for patients with colorectal adenoma (CRA) and CRC. Herein, we undertook a systematic search for citations in PubMed and the Cochrane Database from January 1, 2002 through December 31, 2017 as electronic sources for this study. All published studies were screened with no restriction on language, date, or country. We used database-specific combinations of the following index terms and text words, including: microRNA, colorectal cancer, serum, plasma, and exosomes. Based upon these searches, we summarize the progress and salient features of the current state of knowledge of miRNA diagnostic biomarkers in CRC, and focuses on the articles that attempt to optimize ideal methodologies to further advance their as liquid biopsies for clinical use. We conclude that the field of noncoding RNAs, particularly for the clinical use of miRNAs as liquid biopsy assays is maturing rapidly, and it is highly promising that these genomic signatures will likely be developed into clinically-viable tests for the early detection and clinical management of patients with colorectal cancer in the not so distant future.


Assuntos
Adenoma/diagnóstico , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Adenoma/sangue , MicroRNA Circulante/análise , Neoplasias Colorretais/sangue , Humanos , Biópsia Líquida
8.
Methods Mol Biol ; 1779: 471-484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29886551

RESUMO

Alzheimer's disease is the most common form of dementia and is characterized by a progressive loss of cognitive functions. As the result of predicted demographic changes over the next decades, Alzheimer's disease is expected to be one of the most pressing medical and social challenges facing our generation. Current treatment strategies remain symptomatic. However, new approaches have shown promise in clinical trials, particularly in patients with only mild or moderate symptoms. Early detection of Alzheimer's disease is therefore of critical importance. Currently available diagnostic approaches (such as protein analysis in cerebrospinal fluid or neuroimaging), however, are expensive and invasive and therefore unsuitable for the screening of a large population. Consequently, Alzheimer's disease is generally diagnosed too late for effective intervention. MicroRNAs-readily measurable in biofluids and resistant to freeze-thaw and pH changes, have shown encouraging diagnostic potential in Alzheimer's disease. Several studies have attempted to correlate changes of specific microRNAs to disease progression using different approaches and profiling platforms including micro-arrays, RNA sequencing, and qPCR-based systems. In the present book chapter, we will describe the different steps involved in how to determine the microRNA profile in plasma samples from patients using the OpenArray platform.


Assuntos
Doença de Alzheimer/genética , Biomarcadores/análise , MicroRNA Circulante/análise , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Doença de Alzheimer/sangue , Biomarcadores/sangue , Diagnóstico Precoce , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
9.
Anal Chem ; 90(11): 6618-6625, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29730931

RESUMO

In this paper, an on-line solid-phase extraction capillary electrophoresis-mass spectrometry (SPE-CE-MS) method is described for the purification, preconcentration, separation, and characterization of endogenous microRNA (miRNA) and their post-transcriptional modifications in serum. First, analysis by CE-MS was optimized using a standard mixture of hsa-miR-21-5p (miR-21-5p) and hsa-let-7g-5p (let-7g-5p). For SPE-CE-MS, a commercial silicon carbide (SiC) resin was used to prepare the microcartridges. Under the optimized conditions with standards, the microcartridge lifetime (>25 analyses) and repeatability (2.8% RSD for the migration times; 4.4 and 6.4% RSD for the miR-21-5p and let-7g-5p peak areas, respectively) were good, the method was linear between 25 and 100 nmol·L-1, and the limit of detection (LOD) was around 10 nmol·L-1 (50 times lower than by CE-MS). In order to analyze human serum samples, an off-line sample pretreatment based on phenol/chloroform/isoamyl alcohol (PCA) extraction was necessary prior to SPE-CE-MS. The potential of the SPE-CE-MS method to screen for B-cell chronic lymphocytic leukemia (CLL) was demonstrated by an analysis of serum samples from healthy controls and patients. MicroRNAs, specifically miR-21-5p and a 23 nucleotide long 5'-phosphorylated miRNA with 3'-uridylation (iso-miR-16-5p), were only detected in the CLL patients.


Assuntos
MicroRNA Circulante/análise , Espectrometria de Massas , Neoplasias/química , Extração em Fase Sólida , MicroRNA Circulante/metabolismo , Eletroforese Capilar , Humanos , Neoplasias/sangue , Neoplasias/metabolismo , Processamento de Proteína Pós-Traducional
10.
Med Sci Monit ; 24: 2031-2037, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29622762

RESUMO

BACKGROUND D-dimer tests have been widely used to rule-out deep venous thrombosis (DVT), but with low specificity. Circulating microRNAs (miRNAs) are novel promising biomarkers in diverse diseases. The purpose of our study was to identify the diagnostic abilities of circulating miRNA-320a/b and to assess their correlation with plasma D-dimer in DVT and post-thrombotic syndrome (PTS) patients. MATERIAL AND METHODS Plasma samples were taken from 30 DVT patients, 30 PTS patients, and 30 age- and sex-matched healthy volunteers. Quantitative real-time PCR (qPCR) assay and turbidimetric immunoassay were conducted to assess the concentrations of miRNA-320a/b and D-dimer in plasma. RESULTS Circulating miRNA-320a and miRNA-320b were significantly upregulated in DVT patients with fold changes of 1.58 and 1.79, respectively. The receiver operating characteristic (ROC) curve analysis showed area under the curve (AUC) values of 0.70 (95% CI: 0.56-0.83) for miRNA-320a and 0.79 (95% CI: 0.67-0.90) for miRNA-320b. Moreover, plasma levels of miRNA-320b were associated with D-dimer values (r=0.52, 95% CI: 0.19-0.74) in DVT. However, no significant changes in plasma miRNA-320a/b and D-dimer were detected in PTS patients. CONCLUSIONS Compared with controls, circulating miRNA-320a/b was differentially expressed in DVT. Simultaneous detection of miRNA-320a/b with D-dimer may improve diagnostic accuracy of DVT.


Assuntos
MicroRNA Circulante/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose Venosa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , MicroRNA Circulante/sangue , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Transcriptoma/genética , Trombose Venosa/sangue , Trombose Venosa/genética
11.
World J Gastroenterol ; 24(15): 1601-1615, 2018 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-29686467

RESUMO

This review intends to uncover how information from large-scale genetic profiling (whole genome sequencing, and whole exome sequencing) of nonalcoholic fatty liver disease (NAFLD), as well as information from circulating transcriptomics (cell-free miRNAs) and metabolomics, contributes to the understanding of NAFLD pathogenesis. A further aim is to address the question of whether OMICs information is ready to be implemented in the clinics. The available evidence suggests that any new knowledge pertaining to molecular signatures associated with NAFLD and nonalcoholic steatohepatitis should be promptly translated into the clinical setting. Nevertheless, rigorous steps that must include validation and replication are mandatory before utilizing OMICs biomarkers in diagnostics to identify patients at risk of advanced disease, including liver cancer.


Assuntos
MicroRNA Circulante/análise , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Biomarcadores/análise , Biópsia , MicroRNA Circulante/genética , Progressão da Doença , Humanos , Fígado/patologia , Metabolômica/métodos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Risco , Índice de Gravidade de Doença , Sequenciamento Completo do Exoma/métodos
12.
Microrna ; 7(2): 138-147, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29658445

RESUMO

BACKGROUND: The measurement of circulating miRNAs has proven to be a powerful biomarker tool for several disease processes. Current protocols for the detection of miRNAs usually involve an RNA extraction step, requiring a substantial volume of patient serum or plasma to obtain sufficient input material. OBJECTIVE: Here, we describe a novel methodology that allows detection of a large number of miRNAs from a small volume of serum or plasma without the need for RNA extraction. METHODS: Three µl of serum or plasma was subjected to three cycles of high and low temperatures (heat/freeze cycles) followed by miRNA arrays. RESULTS: Our results indicate that miRNA detection following this process is highly reproducible when comparing multiple samples from the same subject. Moreover, this protocol increases the reproducibility of miRNA detection in samples that were previously subjected to multiple freeze-thaw cycles. Importantly, the detection of miRNAs from serum vs. plasma following heat/freeze cycling are highly comparable, indicating that this heat/freeze process effectively eliminates differences in detection between serum and plasma samples that have been reported using other sample preparation methodologies. CONCLUSION: We propose that this method is a potent alternative to current RNA extraction protocols, substantially reducing the amount of sample necessary for miRNA detection while simultaneously improving miRNA detection and reproducibility.


Assuntos
Biomarcadores/análise , MicroRNA Circulante/análise , Plasma/química , Soro/química , Manejo de Espécimes/métodos , Congelamento , Temperatura Alta , Humanos
13.
Acta Neurol Scand ; 138(2): 130-136, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29527713

RESUMO

BACKGROUND: Biomarkers that could be used in early diagnosis of multiple sclerosis (MS), segregation of disease subtypes, and discrimination of the aggressive disease course from the benign one are urgently needed. OBJECTIVE: The aim of this study was to investigate the specificity of circulating microRNAs: miR-191-5p, miR-128-3p, miR-24-3p, and miR-376c-3p in MS and evaluate their association with disease activity and disability progression. METHODS: The expressions of circulating miRNAs were studied in serum of 100 subjects (53 relapsing-remitting (RRMS), 20 primary progressive (PPMS), and 27 controls), using miScript serum miRNA RT-PCR assay techniques. RESULTS: In comparison with controls, miR-191-5p and miR-24-3p were overexpressed in RRMS and PPMS, with no differences between the subtypes. miR-24-3p correlated positively with the disability progression index in the combined group of all patients with MS. miR-128-3p showed tendency toward the predominant expression in PPMS and correlated positively with the annual relapse rate in RRMS. miR-376c-3p expression levels did not differ between the groups, and no associations were found to clinical parameters. CONCLUSION: This study highlighted the connection of circulating miRNAs to MS. miR-24-3p and miR-128-3p showed a tendency of association with disability accumulation and disease activity, respectively. Further studies should evaluate their suitability for clinical use.


Assuntos
Biomarcadores/sangue , MicroRNA Circulante/análise , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico , Adulto , MicroRNA Circulante/sangue , Progressão da Doença , Feminino , Humanos , Masculino , MicroRNAs/análise , MicroRNAs/sangue , Pessoa de Meia-Idade , Adulto Jovem
14.
Sci Rep ; 8(1): 4867, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29559644

RESUMO

The assessment of bone quality and the prediction of fracture risk in idiopathic osteoporosis (IOP) are complex prospects as bone mineral density (BMD) and bone turnover markers (BTM) do not indicate fracture-risk. MicroRNAs (miRNAs) are promising new biomarkers for bone diseases, but the current understanding of the biological information contained in the variability of miRNAs is limited. Here, we investigated the association between serum-levels of 19 miRNA biomarkers of idiopathic osteoporosis to bone microstructure and bone histomorphometry based upon bone biopsies and µCT (9.3 µm) scans from 36 patients. Four miRNAs were found to be correlated to bone microarchitecture and seven miRNAs to dynamic histomorphometry (p < 0.05). Three miRNAs, namely, miR-29b-3p, miR-324-3p, and miR-550a-3p showed significant correlations to histomorphometric parameters of bone formation as well as microstructure parameters. miR-29b-3p and miR-324-p were found to be reduced in patients undergoing anti-resorptive therapy. This is the first study to report that serum levels of bone-related miRNAs might be surrogates of dynamic histomorphometry and potentially reveal changes in bone microstructure. Although these findings enhance the potential value of circulating miRNAs as bone biomarkers, further experimental studies are required to qualify the clinical utility of miRNAs to reflect dynamic changes in bone formation and microstructure.


Assuntos
Osso e Ossos/patologia , Osteoporose Pós-Menopausa/genética , Osteoporose/genética , Adulto , Biomarcadores/sangue , Densidade Óssea/genética , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , MicroRNA Circulante/análise , MicroRNA Circulante/genética , Estudos Transversais , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Osteogênese/genética , Osteogênese/fisiologia , Osteoporose/sangue , Osteoporose/metabolismo , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/metabolismo , Fraturas por Osteoporose/genética , Fatores de Risco
15.
Carcinogenesis ; 39(4): 556-561, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29471417

RESUMO

Prostate cancer is one of the most common cancers in men worldwide. Currently available diagnostic and prognostic tools for this disease, such as prostate specific antigen, suffer from lack of specificity and sensitivity, resulting in over- and misdiagnosis. Hence, there is an urgent need for clinically relevant biomarkers capable of distinguishing between aggressive and nonaggressive forms of prostate cancer to aid in stratification, management and therapeutic decisions. To address this unmet need, we investigated the patterns of expression of a panel of 68 plasma-derived microRNAs (miRNAs) in a cohort of African American (AA) and European American (EA) prostate cancer patients (n = 114). miRNA qPCR results were analyzed using in-depth statistical methods, and a bioinformatics analysis was conducted to identify potential targets of the differentially expressed miRNAs. Our data demonstrate that a new previously unreported circulating miRNA signature consisting of a combination of interacting miRNAs (miR-17/miR-192) and an independent miRNA (miR-181a) are capable of segregating aggressive and nonaggressive prostate cancer in both AA and EA patients. The interacting miRNAs outperformed independent miRNAs in identifying aggressiveness. Our results suggest that these circulating miRNAs may constitute novel biomarkers of prostate cancer aggressiveness in both races and warrant further investigation.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Neoplasias da Próstata/sangue , Adulto , Idoso , Biomarcadores Tumorais/genética , MicroRNA Circulante/análise , MicroRNA Circulante/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
16.
Metabolism ; 86: 49-60, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29410349

RESUMO

PURPOSE: Circulating micro-ribonucleic acids (miRNAs) are small noncoding RNA molecules that influence gene transcription. We conducted the present profiling study to characterize the expression of circulating miRNAs in lean and obese patients with polycystic ovary syndrome (PCOS), the most common endocrine and metabolic disorder in premenopausal women. BASIC PROCEDURES: We selected 11 control women, 12 patients with PCOS and 12 men so that they were similar in terms of body mass index. Five control women, 6 men and 6 patients with PCOS had normal weight whereas 6 subjects per group were obese. We used miRCURY LNA™ Universal RT microRNA PCR for miRNA profiling. MAIN FINDINGS: The expression of 38 miRNAs and was different between subjects with PCOS and male and female controls. The differences in 15 miRNAs followed a pattern suggestive of androgenization characterized by expression levels that were similar in patients with PCOS and men but were different compared with those of control women. The expression of 13 miRNAs in women with PCOS was similar to that of control women and different compared with the expression observed in men, suggesting sexual dimorphism and, lastly, we observed 5 miRNAs that were expressed differently in women with PCOS compared with both men and control women, suggesting a specific abnormality in expression associated with the syndrome. Obesity interacted with the differences in several of these miRNAs, and the expression levels of many of them correlated with the hirsutism score, sex hormones and/or indexes of obesity, adiposity and metabolic dysfunction. PRINCIPAL CONCLUSIONS: The present results suggest that several serum miRNAs are influenced by PCOS, sex hormones and obesity. Our findings may guide the targeted search of miRNAs as clinically relevant markers for PCOS and its association with obesity and metabolic dysfunction in future studies.


Assuntos
MicroRNA Circulante/análise , Hormônios Esteroides Gonadais/sangue , Obesidade/genética , Síndrome do Ovário Policístico/genética , Adulto , Estudos de Casos e Controles , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Feminino , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Humanos , Masculino , Obesidade/sangue , Obesidade/complicações , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Transcriptoma/efeitos dos fármacos , Adulto Jovem
17.
Biomarkers ; 23(4): 339-346, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29378466

RESUMO

BACKGROUND: Circulating miRNAs as potential non-invasive biomarkers for disease risk assessment and cancer early diagnosis have attracted increasing interest. Little information, however, is available regarding the intra-individual variation of circulating miRNA levels. METHODS: We measured expression levels of a panel of 800 miRNAs in repeated plasma samples from 51 healthy individuals that were collected 6 to 12 months apart and evaluated the intra-individual variation by the intra-class correlation coefficient (ICC). RESULTS: After background correction, a total of 185 miRNAs were detected in at least 10% of the plasma samples, with 69 and 28 miRNAs being detected in 50% and 90% of samples, respectively. The median ICC was 0.46 for these 185 miRNAs. Among them, 41% (75 miRNAs) had an ICC ≥ 0.5, and 23% (42 miRNAs) had an ICC ≥ 0.6. The ICC is higher for miRNAs with higher expression levels or higher detection rates, when compared to those with lower expression levels or lower detection rates. CONCLUSIONS: These results suggest that common circulating miRNAs are stable over a relatively long period and can serve as reliable biomarkers for epidemiological and clinical research.


Assuntos
MicroRNA Circulante/análise , MicroRNAs/sangue , Biomarcadores/sangue , Voluntários Saudáveis , Humanos , Estabilidade de RNA , Fatores de Tempo
18.
Leg Med (Tokyo) ; 31: 7-9, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29220722

RESUMO

Sudden and unexpected death in epilepsy (SUDEP) represents one of the most challenging fields for clinical, forensic and preventative pathology. Several authors have emphasized the search of innovative biomarkers related to drug-resistance for an appropriate risk stratification in these patients. However, no reliable biomarker has been implemented into clinical practice, so far. Herein, we present a case of SUDEP due to drug-resistant mesial temporal lobe epilepsy (MTLE) in which we performed miRNA expression profiling (miR-301a-3p, miR-194-5p, miR-30b-5p, mIR-342-5p, and miR-4446-3p) from both the plasma and the temporal lobe in comparison to ten autopsies for traumatic or asphyxia deaths. A significant up-regulation of miR-301a-3p in both the plasma (2.3 increase vs. controls) and the hippocampus (3.2-fold increase vs. controls) was evidenced, whereas the other tested miRNAs showed no significant expression differences between case and controls. Even preliminary, our results support miRNAs as an innovative class of biomarkers compatible with an adequate analysis of biospecimens obtained from forensic autopsies.


Assuntos
MicroRNA Circulante/análise , Morte Súbita/etiologia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/genética , Biomarcadores , Bases de Dados Genéticas , Feminino , Humanos , Adulto Jovem
19.
J Cell Biochem ; 119(7): 5262-5273, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29266445

RESUMO

This study aims to elucidate the prognostic and predictive biomarker of miR-495 and Stat3 in peripheral blood in relation to lower extremity deep venous thrombosis (DVT). Patients with lower limb fractures were assigned into case and control groups. Rats were allocated into blank (normal rats), sham (normal rats), DVT, miR-495 mimic, miR-495 inhibitor, over-Stat3, and si-Stat3 groups. ELISA was used to detect levels of prothrombin time (PT), endothelin-1 (ET-1), Human Fibrinogen (FIB), D-Dimer, blood coagulation factors V and VIII, tissue type plasminogen activator (t-PA), platelet activating factor (PAF), protein C and Stat3. qRT-PCR was employed for the evaluation of the expressions of miR-495 and Stat3, while receiver operating characteristic (ROC) curve was constructed to assess the predictive value of miR-495 and Stat3 as well as the treatment outcomes of patients with lower limb fractures. Logistic regression analyses were conducted in order to correlate indexes and lower extremity DVT. miR-495 overexpression, t-PA, PAF, and protein C were confirmed to be protective factors, while Stat3 overexpression, PT, ET-1, FIB, D-Dimer, blood coagulation factor V, and VIII were all ultimately considered to be risk factors of lower extremity DVT. Stat3 was confirmed to be the target gene of miR-495. Compared with the blank group, the length and weight of the thrombus as well as the ratio between length and weight, mRNA and protein expression of Stat3 were reduced in the miR-495 mimic and si-Stat3 groups. Our findings suggest that through the suppression of Stat3 expression, miR-495 prohibits lower extremity DVT in peripheral blood.


Assuntos
Biomarcadores/sangue , MicroRNA Circulante/análise , Extremidade Inferior/patologia , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Trombose Venosa/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Trombose Venosa/sangue , Trombose Venosa/genética , Adulto Jovem
20.
J Neurotrauma ; 35(1): 64-72, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28762893

RESUMO

To assess the accuracy and physiological relevance of circulating microRNA (miRNA) as a biomarker of pediatric concussion, we compared changes in salivary miRNA and cerebrospinal fluid (CSF) miRNA concentrations after childhood traumatic brain injury (TBI). A case-cohort design was used to compare longitudinal miRNA concentrations in CSF of seven children with severe TBI against three controls without TBI. The miRNAs "altered" in CSF were interrogated in saliva of 60 children with mild TBI and compared with 18 age- and sex-matched controls. The miRNAs with parallel changes (Wilcoxon rank sum test) in CSF and saliva were interrogated for predictive accuracy of TBI status using a multivariate regression technique. Spearman rank correlation identified relationships between miRNAs of interest and clinical features. Functional analysis with DIANA mirPath identified related mRNA pathways. There were 214 miRNAs detected in CSF, and 135 (63%) were also present in saliva. Six miRNAs had parallel changes in both CSF and saliva (miR-182-5p, miR-221-3p, mir-26b-5p, miR-320c, miR-29c-3p, miR-30e-5p). These miRNAs demonstrated an area under the curve of 0.852 for identifying mild TBI status. Three of the miRNAs exhibited longitudinal trends in CSF and/or saliva after TBI, and all three targeted mRNAs related to neuronal development. Concentrations of miR-320c were directly correlated with child and parent reports of attention difficulty. Salivary miRNA represents an easily measured, physiologically relevant, and accurate potential biomarker for TBI. Further studies assessing the influence of orthopedic injury and exercise on peripheral miRNA patterns are needed.


Assuntos
Biomarcadores/análise , Concussão Encefálica/diagnóstico , Líquido Cefalorraquidiano/química , MicroRNA Circulante/análise , Saliva/química , Criança , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Transcriptoma
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