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1.
Medicine (Baltimore) ; 100(4): e22946, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530155

RESUMEN

ABSTRACT: The present study aimed to investigate the correlation of long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) with microRNA (miR)-21, miR-124, and miR-125a, and their associations with disease risk, severity, and inflammatory cytokines of allergic rhinitis (AR).Totally 70 AR patients and 70 non-atopic obstructive snoring patients (as controls) were recruited. Inferior turbinate mucosa samples were collected from all participants for lncRNA NEAT1, its targets (miR-21, miR-124, and miR-125a), interleukin (IL)-4, IL-6, IL-10, and IL-17 detection via reverse transcription quantitative polymerase chain reaction. Disease severity of AR patients was assessed using individual nasal symptom score (INSS) and total nasal symptom score (TNSS).LncRNA NEAT1 was upregulated, while miR-21, miR-124, and miR-125a were downregulated in AR patients compared with controls. Additionally, lncRNA NEAT1, miR-21, and miR-125a displayed good values in differentiating AR patients from controls, while miR-124 could only slightly differentiate AR patients from controls. In AR patients, lncRNA NEAT1 was negatively associated with miR-21 and miR-125a, but not miR-124. However, in controls, no correlation of lncRNA NEAT1 with miR-21, miR-124, or miR-125a was observed. Furthermore, in AR patients, lncRNA NEAT1 was positively, while miR-21 and miR-125a was negatively associated with INSS (rhinorrhea, itching, congestion scores), TNSS and inflammatory cytokines; however, correlation of miR-124 with INSS, TNSS, and inflammatory cytokines was slight.LncRNA NEAT1 and its targets (miR-21 and miR-125a) present close correlations with disease risk, severity, and inflammation of AR, suggesting their potential as biomarkers for AR assessment.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , MicroARNs/sangre , ARN Largo no Codificante/sangre , Rinitis Alérgica/genética , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Inflamación/genética , Masculino , Rinitis Alérgica/sangre , Índice de Severidad de la Enfermedad
2.
Biomed Environ Sci ; 34(1): 19-28, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33531104

RESUMEN

Objective: In the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD. Methods: This is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects. Results: The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs ( P < 0.05). The levels of ABCA1-labeled exosomal miR-135a increased in the CSF of MCI and DAT group compared to those of control group ( P < 0.05), slightly increased ( P > 0.05) in the serum of SCD patient group, and significantly increased in MCI and DAT patient groups compared to those of the control group ( P < 0.05). Conclusion: This study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD.


Asunto(s)
Transportador 1 de Casete de Unión a ATP , Disfunción Cognitiva/sangre , Exosomas , MicroARNs/sangre , Transportador 1 de Casete de Unión a ATP/sangre , Transportador 1 de Casete de Unión a ATP/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Animales , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Línea Celular , Disfunción Cognitiva/líquido cefalorraquídeo , Eritrocitos/metabolismo , Femenino , Humanos , Leucocitos/metabolismo , Masculino , Ratones Transgénicos , Neuronas/metabolismo
3.
Int J Nanomedicine ; 16: 371-381, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33469291

RESUMEN

Purpose: Efficient approaches to reliably improving wound healing in diabetic patients remain to be developed. Exosomes are nanomaterials from which therapeutically active microRNAs (miRNAs) can be isolated. In the present report, we therefore isolated circulating exosome-derived miRNAs from patients with diabetes and assessed the impact of these molecules on wound healing. Patients and Methods: Exosomes were isolated from the serum of control or diabetic patients (Con-Exos and Dia-Exos, respectively), after which the effects of these exosomes on cellular activity and wound healing were assessed. Results: We determined that miR-20b-5p was overexpressed in Dia-Exos and that it functioned by impairing wound repair by suppressing vascular endothelial growth factor A (VEGFA) expression. Consistent with such a model, the administration of Dia-Exos or this miRNA both in vivo and in vitro was sufficient to slow wound repair. Conclusion: Dia-Exos exhibit significant increases in miR-20b-5p relative to Con-Exos, and this miRNA can be transferred into HSFs wherein it can suppress VEGFA expression and thereby slow the process of wound healing.


Asunto(s)
Diabetes Mellitus/genética , Diabetes Mellitus/patología , Exosomas/metabolismo , MicroARNs/sangre , MicroARNs/genética , Cicatrización de Heridas , Animales , Secuencia de Bases , Exosomas/ultraestructura , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Masculino , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
4.
J Urol ; 205(1): 137-144, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32856980

RESUMEN

PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/ß-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.


Asunto(s)
Biomarcadores de Tumor/sangre , MicroARN Circulante/sangre , MicroARNs/sangre , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Orquiectomía , Neoplasias Testiculares/diagnóstico , Adulto , Estudios de Casos y Controles , Quimioterapia Adyuvante , Toma de Decisiones Clínicas/métodos , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/sangre , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Periodo Preoperatorio , Neoplasias Testiculares/sangre , Neoplasias Testiculares/patología , Neoplasias Testiculares/terapia , Testículo/patología , Testículo/cirugía , Espera Vigilante
5.
J Surg Res ; 257: 203-212, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32858321

RESUMEN

BACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears' ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression.


Asunto(s)
Hemostasis/genética , Hibernación/genética , MicroARNs/metabolismo , Ursidae/genética , Tromboembolia Venosa/genética , Animales , Antitrombina III/genética , Línea Celular Tumoral , Femenino , Silenciador del Gen , Hepatocitos , Humanos , Masculino , MicroARNs/sangre , Estaciones del Año , Regulación hacia Arriba , Ursidae/sangre , Tromboembolia Venosa/prevención & control
6.
Eur J Endocrinol ; 184(1): 41-49, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33112286

RESUMEN

Objective: In insulin-like growth factor II (IGF-II) producing non-islet cell tumor hypoglycemia (NICTH), high molecular weight forms of IGF-II (big IGF-II) are produced as a cause of spontaneous hypoglycemia. MicroRNA (miRNA)-483 family, encoded in an intron lesion of IGF2 gene, is suggested to be co-expressed with IGF-II. Here, we tested whether serum miR-483-5p and -3p levels are associated with the presence of big IGF-II in NICTH. Design: Serum samples from patients who were suspected to have IGF-II producing NICTH (n = 42) were tested. MiR-483-5p and -3p levels were evaluated using quantitative PCR. IGF-II level was analyzed using ELISA. The presence of big IGF-II was identified by Western blotting. Results: Big IGF-II was detected in the sera of 32 patients. MiR-483-5p (P = 0.0015) and -3p (P = 0.027) levels were significantly higher in sera with big IGF-II (n = 32) than in those without (n = 10), whereas serum IGF-II level (P = 0.055) was not significantly different between the groups. The median serum concentration of miR-483-5p was ~10 times higher than that of miR-483-3p. Although a strong correlation was observed between the two miRNAs (r = 0.844, P < 0.0001), but neither of which was correlated with serum IGF-II level. The areas under the receiver operating characteristic curves of miR-483-5p (0.853) and -3p (0.722) were higher than that of IGF-II (0.694) for detecting the presence of big IGF-II. Conclusion: The associations of serum miR-483-5p and -3p levels with the presence of big IGF-II suggest the diagnostic potential of these miRNAs for IGF-II producing NICTH.


Asunto(s)
Hipoglucemia/diagnóstico , Factor II del Crecimiento Similar a la Insulina/metabolismo , MicroARNs/sangre , Neoplasias/sangre , Anciano , Área Bajo la Curva , Western Blotting , Femenino , Humanos , Hipoglucemia/etiología , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/genética , Curva ROC
7.
Viruses ; 12(12)2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33327640

RESUMEN

Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.


Asunto(s)
Biomarcadores , Hepacivirus , Virus de la Hepatitis B , Hepatitis B/genética , Hepatitis B/virología , Hepatitis C/genética , Hepatitis C/virología , MicroARNs/genética , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Hepatitis B/complicaciones , Hepatitis B/diagnóstico , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , MicroARNs/sangre , Pronóstico , Replicación Viral
8.
J Cancer Res Ther ; 16(6): 1223-1228, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33342777

RESUMEN

Background: MicroRNAs (miRNAs) are involved in the regulation of genes with important roles in cancer. Therefore, they represent interesting targets as biomarkers for early detection, follow-up, and prognosis of the disease. Context: In early stages of breast cancer, differences in the expression of miR-148b-3p, miR-145-5p and miR-133a-3p have been reported. Aims: To compare the expression of miR-148b-3p, miR-145-5p and miR-133a-3p in serum samples from female patients with and without breast cancer. Setting and Design: Case control study. Materials and Methods: We quantified the expression by real-time polymerase chain reaction of miR-148b-3p, miR-145-5p, and miR-133a-3p in serum samples from 27 breast cancer (BC) and 17 benign breast tumor patients. Statistical Analysis Used: Comparison between groups with categorical variables was made using the Pearson's Chi-square test. Comparative analysis for continuous variables between two groups was performed using the Student's t-test. One-way analysis of variance (ANOVA) was used for multigroup comparison, followed by Tukey HSD analysis. Results: The use of contraceptives and a high number of births were identified as risk factors for BC. We observed that miR-145-5p expresses in low levels in BC and positively diagnosed Her2 patients. In addition, BC patients with either ductal carcinoma or positive molecular diagnosis for estrogen receptor, progesterone receptor, luminal A, or Her2 negative, presented a decreased expression of miR-133a-3p. Conclusions: We observed an existing association between the molecular characteristics of BC and levels of circulating miR-133a-3p and miR-145-5p, proving the potential role of miRNAs as biomarkers for BC.


Asunto(s)
Neoplasias de la Mama/sangre , MicroARNs/biosíntesis , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Receptores Estrogénicos/metabolismo , Receptores de Progesterona/metabolismo
9.
Medicine (Baltimore) ; 99(50): e23444, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33327275

RESUMEN

This study aimed to investigate the correlation of long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) with microRNA-223 (miR-223) as well as their associations with risk, severity, and mortality of sepsis.Totally122 sepsis patients and 122 healthy controls were enrolled. Plasma lncRNA TUG1 and miR-223 levels were detected by reverse transcription quantitative polymerase chain reaction. General severity of sepsis was assessed within 24 hours after admission using acute pathologic and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score. Patients were intensively followed up until death or 28 days after enrollment to assess mortality.LncRNA TUG1 expression was decreased (P < .001) but miR-223 expression (P < .001) was elevated in sepsis patients. Additionally, a negative correlation of lncRNA TUG1 expression with miR-223 expression was observed in sepsis patients (P < .001). Moreover, in sepsis patients, lncRNA TUG1 expression was negatively correlated with respiratory infection, serum creatinine (Scr), white blood cell (WBC), C-reactive protein (CRP), APACHE II score, and SOFA score but positively correlated with albumin (all P < .05); miR-223 expression was negatively correlated with skin and soft tissue infection and albumin but positively correlated with Scr, WBC, CRP, APACHE II score, and SOFA score (all P < 0.05). As to mortality, lncRNA TUG1 expression was decreased (P = .001) but miR-223 was elevated (P < .001) in 28-day sepsis deaths compared with 28-day sepsis survivors.Our findings offer the potential of lncRNA TUG1 and miR-223 as biomarkers for progression and prognosis of sepsis.


Asunto(s)
MicroARNs/sangre , ARN Largo no Codificante/sangre , Sepsis/genética , Sepsis/mortalidad , APACHE , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Factores de Riesgo , Tasa de Supervivencia
10.
Medicine (Baltimore) ; 99(50): e23599, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33327325

RESUMEN

BACKGROUND: Previous studies have reported that microRNA-203 has an effect on the prognosis of with esophageal cancer (EC). However, the conclusion is remains controversial. Therefore, this study will try to explore the effect of high expression of microRNA-203 on the prognosis of EC patients. METHODS: Eligible studies were searched from Google Scholar, Embase, PubMed, Medline, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Scientific Journal Database, Chinese BioMedical Database and Wanfang Database. Papers in English or Chinese published from their inception to November 2020 will be included without any restrictions. Stata 14.0 and Review Manager 5.3 software were used for data analysis. Hazard ratios (HRs) and its 95% confidence intervals (CIs) were used to assess the prognostic effect of microRNA-203 on overall survival (OS) and disease-free survival (DFS). Methodological quality for each eligible trial will be assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOS). RESULTS: This study will provide a high-quality evidence-based medical evidence of the correlations between microRNA-203 expression and OS and DFS. CONCLUSION: The findings of this meta-analysis will show the effect of high expression of microRNA-203 on the prognosis of EC patients, and may find a new prognostic marker for EC. INPLASY REGISTRATION NUMBER: INPLASY2020110022.


Asunto(s)
Neoplasias Esofágicas/diagnóstico , MicroARNs/sangre , Biomarcadores de Tumor/sangre , Neoplasias Esofágicas/sangre , Humanos
11.
Medicine (Baltimore) ; 99(52): e23863, 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33350781

RESUMEN

ABSTRACT: To identify serum microRNA-25 (miR-25) as a diagnostic biomarker for pancreatic cancer (PCa) and to evaluate its supplementary role with serum carbohydrate antigen 19-9 (CA19-9) in early identification of cancers.Eighty patients with pancreatic cancer and 91 non-cancer controls were enrolled in this study. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of miR-25. Levels of CA19-9, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) were measured by chemiluminescent immunoassay. The logistic model was established to evaluate the correlation of miR-25 with clinical characteristics. A risk model for PCa was conducted by R statistical software. Diagnostic utility for PCa and correlation with clinical characteristics were analyzed.The expression level of miR-25, in the PCa group was significantly higher (P < .05). Risk Model illustrated the relation between miR-25 and pancreatic cancer. With the combination of CA19-9, the performance of miR-25 in early stages (I+II) in the diagnosis of PCa was profoundly better than CA19-9 and miR-25 alone. This combination was more effective for discriminating PCa from non-cancer controls (AUC-ROC, 0.985; sensitivity, 97.50%; specificity, 90.11%) compared with CA19-9 alone or the combination of CA19-9 and CA125.The expression level of miR-25 among pancreatic cancer patients was significantly higher than that in the control group. miR-25 existed as one of the most relevant factors of PCa. miR-25 can serve as a novel noninvasive approach for PCa diagnosis, and with the supplementary of CA19-9, the combination was more effective, especially in early tumor screening.


Asunto(s)
Antígeno CA-19-9/sangre , MicroARNs/sangre , Neoplasias Pancreáticas , Medición de Riesgo/métodos , Biomarcadores de Tumor/sangre , Diagnóstico Diferencial , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Reproducibilidad de los Resultados
12.
Medicine (Baltimore) ; 99(51): e23425, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33371070

RESUMEN

OBJECTIVE: Previous studies have shown that microRNA-25 (miR-25) plays a key role in the occurrence and development of non-small cell lung cancer (NSCLC). Many studies have shown that there is a significant increment of miR-25 in circulating blood of patients with NSCLC. The meta-analysis aims to explore diagnostic value of miR-25 in NSCLC in Chinese population. METHODS: PubMed, Web of science, Excerpta Medica Database, China national knowledge infrastructure and China Wanfang database were searched to collect studies upon correlation between miR-25 and diagnosis of the patients with NSCLC until April 2020. Combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristic curve were calculated by Stata 15.0 software. Literature assessment was conducted according to quality assessment of diagnostic accuracy studies, and documents with scores above or equal to 11 were included in this meta-analysis. RESULTS: Six studies were included, including 480 cases with NSCLC and 451 healthy controls. The combined sensitivity (0.75, 95% confidence interval [CI]: 0.69∼0.80), specificity (0.81, 95% CI: 0.76∼0.86), positive likelihood ratio (4.04, 95% CI: 3.14∼5.20), negative likelihood ratio (0.31, 95% CI: 0.25∼0.37), diagnostic odds ratio (13.09, 95% CI: 9.37∼18.29) and area under curve (0.85, 95% CI: 0.82∼0.88) indicated that miR-25 had desirable diagnostic accuracy for NSCLC. CONCLUSION: MiR-25 can be applied in diagnosis of NSCLC and has potential of becoming a biomarker for detection of patients with early NSCLC in Chinese population.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , MicroARNs/sangre , Grupo de Ascendencia Continental Asiática , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/etnología , China , Humanos , Neoplasias Pulmonares/etnología , Sensibilidad y Especificidad
13.
Medicine (Baltimore) ; 99(40): e22444, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019429

RESUMEN

BACKGROUND AND OBJECTIVE: miRNA-146a is a microRNA that plays an important role in systemic lupus erythematosus (SLE). Several studies have examined the role of miRNA-146a in SLE, but have demonstrated equivocal or even contradictory conclusions. Therefore, this meta-analysis aimed to assess the role of miRNA-146a in SLE by examining data from previous studies. METHODS: A meta-analysis of relevant papers published before August 31, 2019, in the WanFang, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and Web of Science databases was performed to verify the relationship of miRNA-146a expression level to SLE. Two investigators independently extracted the data and conducted a quality assessment of the studies. All statistical analyses were performed using Stata 14.0. Trial sequence analysis (TSA) was conducted to assess the quality and strength of the studies using the TSA software. RESULTS: Six publications, involving 151 SEL patients and 132 healthy individuals as controls were included in this meta-analysis. The results showed that the expression of miRNA-146a was associated with SLE risk [standard mean difference (SMD) = -1.21, 95% confidence interval (95% CI) (-2.18, -0.23), P = .015]. The stratified analysis revealed that the expression of miRNA-146a was highly related to higher SLE risk among Asian (SMD = -1.30, 95% CI (-2.52, -0.07), P = .038) and Caucasian (SMD = -0.72, 95% CI (-1.20, -0.24), P = .003) populations. Besides, the serum levels of miRNA146a were significantly different (SMD = -1.73, 95% CI (-3.11, -0.36), P = .014). The TSA revealed that the cumulative Z-curve crossed the typical boundary value, and reached the TSA monitoring boundary, but did not reach the required information size. This indicates that even if the cumulative sample size did not meet required information size, no more trials were needed and a reliable conclusion was reached in advance. Sensitivity analyses indicated the instability of the meta-analysis. CONCLUSIONS: Overall, the expression of miRNA-146a is associated with SLE risk. Therefore, miRNA-146a is a promising candidate for the effective diagnosis of SLE. But, due to the limitations of this study, it is necessary to cautiously explain the results of this study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019151381.


Asunto(s)
Lupus Eritematoso Sistémico/genética , MicroARNs/sangre , Estudios de Casos y Controles , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos
14.
PLoS One ; 15(9): e0239386, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32960907

RESUMEN

While tumor resection and liver transplantation (LT) represent potentially curative therapeutic options for patients with early-stage hepatocellular carcinoma (HCC), the identification of the ideal surgical candidates has remained challenging. Just recently, miRNA-193a-5p was described as a tumor suppressor in murine and human HCC but only little is known about circulating miRNA-193a-5p in HCC patients. Here, we evaluated serum levels of miR-193a-5p by qPCR in 41 HCC patients undergoing tumor resection (n = 33) or LT (n = 8) and 20 controls. Circulating relative miR-193a-5p levels were significantly elevated in HCC patients compared to healthy controls. While relative miR-193a-5p levels were comparable between patients of different underlying disease etiology and tumor size, high relative miR-193a-5p levels were predictive for the patients' postoperative outcome, which was confirmed in uni- and multivariate Cox-regression analysis. As such, HCC patients with a preoperative relative miR-193a-5p level above the ideal cut-off value (3.57) had a median overall survival (OS) of only 451 days compared to 1158 days in patients with a relative miR-193a-5p level below this cut-off value. Our data support a novel function of miR-193a-5p as a biomarker in early-stage HCC patients that might help to identify the best surgical candidates in terms of postoperative outcome.


Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/sangre , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Curva ROC , Tasa de Supervivencia , Regulación hacia Arriba
15.
Proc Natl Acad Sci U S A ; 117(39): 24213-24223, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32929008

RESUMEN

MicroRNAs (miRNAs) function cell-intrinsically to regulate gene expression by base-pairing to complementary mRNA targets while in association with Argonaute, the effector protein of the miRNA-mediated silencing complex (miRISC). A relatively dilute population of miRNAs can be found extracellularly in body fluids such as human blood plasma and cerebrospinal fluid (CSF). The remarkable stability of circulating miRNAs in such harsh extracellular environments can be attributed to their association with protective macromolecular complexes, including extracellular vesicles (EVs), proteins such as Argonaut 2 (AGO2), or high-density lipoproteins. The precise origins and the potential biological significance of various forms of miRNA-containing extracellular complexes are poorly understood. It is also not known whether extracellular miRNAs in their native state may retain the capacity for miRISC-mediated target RNA binding. To explore the potential functionality of circulating extracellular miRNAs, we comprehensively investigated the association between circulating miRNAs and the miRISC Argonaute AGO2. Using AGO2 immunoprecipitation (IP) followed by small-RNA sequencing, we find that miRNAs in circulation are primarily associated with antibody-accessible miRISC/AGO2 complexes. Moreover, we show that circulating miRNAs can base-pair with a target mimic in a seed-based manner, and that the target-bound AGO2 can be recovered from blood plasma in an ∼1:1 ratio with the respective miRNA. Our findings suggest that miRNAs in circulation are largely contained in functional miRISC/AGO2 complexes under normal physiological conditions. However, we find that, in human CSF, the assortment of certain extracellular miRNAs into free miRISC/AGO2 complexes can be affected by pathological conditions such as amyotrophic lateral sclerosis.


Asunto(s)
Proteínas Argonauta/sangre , MicroARNs/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Proteínas Argonauta/líquido cefalorraquídeo , Emparejamiento Base , Estudios de Casos y Controles , Humanos , Inmunoprecipitación , MicroARNs/líquido cefalorraquídeo
16.
Value Health ; 23(9): 1171-1179, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32940235

RESUMEN

OBJECTIVES: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer. METHODS: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice). The model was evaluated for 25 years with a healthcare perspective and accounted for test characteristics, compliance, disease progression, cancer recurrence, costs, utilities, and mortality. The outcomes measured included incremental cost-effectiveness ratios, cancer stage at diagnosis, and thresholds for significant variables. RESULTS: The miRNA-based screening was found to be cost-effective with an incremental cost-effectiveness ratio of $40 971/quality-adjusted life-year. Key drivers included test costs, test accuracy, cancer incidence, and recurrence risk. Threshold analysis highlights the need for high accuracy of miRNA tests (threshold sensitivity: 68%; threshold specificity: 77%). A perfect compliance to screening would double the cancer diagnosis in early stages compared to the current practice. Probabilistic sensitivity analysis reported the miRNA-based screening to be cost-effective in >95% of iterations for a willingness to pay of $70 000/quality-adjusted life-year (approximately equivalent to 1 gross domestic product/capita) CONCLUSIONS: The miRNA-based screening intervention was found to be cost-effective and is expected to contribute immensely in early diagnosis of cancer by improving screening compliance.


Asunto(s)
Detección Precoz del Cáncer/economía , Endoscopía/economía , Tamizaje Masivo/economía , MicroARNs/economía , Neoplasias Gástricas/diagnóstico , Anciano , Grupo de Ascendencia Continental Asiática , Análisis Costo-Beneficio , Detección Precoz del Cáncer/métodos , Humanos , Estudios Longitudinales , Masculino , Tamizaje Masivo/estadística & datos numéricos , MicroARNs/sangre , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Medición de Riesgo , Sensibilidad y Especificidad , Singapur/epidemiología , Neoplasias Gástricas/epidemiología
17.
Toxicol Lett ; 334: 21-26, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32910981

RESUMEN

MicroRNAs are key regulators of the normal kidney function and development, and altered in acute kidney injury (AKI). However, there is a lack of studies comparing serum and urine miRNA expression in toxic AKI in humans. We aimed to compare the global signature of urinary and serum microRNAs, with and without kidney injury, after human oxalic acid poisoning. We profiled urinary microRNAs in patients who ingested oxalic acid and developed no injury (No AKI n = 3), moderate injury (AKIN2 n = 3) or severe injury (AKIN3 n = 3) and healthy controls (n = 3). We validated a signature of 30 urinary microRNAs identified in the discovery profiling, in a second cohort of individuals exposed to oxalic acid (No AKI n = 15, AKIN2 n=11 & AKIN3 n= 18) and healthy controls (n=-27) and we compared the results with previously published serum data. Global profiling in toxic AKI patients showed a higher expression of urinary microRNAs and lower expression of serum microRNAs. Most urine microRNA in the validation cohort were significantly upregulated (25/30, fold change >2.8 and p < 0.05) in AKIN2/3 patients compared to No AKI. Four urinary microRNAs (miR-191, miR-19b, miR-20a and miR-30b) had good diagnostic performance (AUC greater than 0.8) to predict AKIN2/3 between 4-8 hours post ingestion. Poisoning irrespective of AKI led to significantly lower expression of many microRNAs in serum but relatively few changes in urinary miRNA expression. In conclusion, urinary microRNA signature provides a stronger measure of AKI in oxalic acid poisoning compared to serum microRNA. Kidney injury has the greatest impact on urinary microRNA, while poisoning itself was better reflected in serum miRNA. Plasma and urinary microRNAs signatures provide complementary information in toxic kidney injury.


Asunto(s)
Lesión Renal Aguda/sangre , Lesión Renal Aguda/orina , MicroARNs , Ácido Oxálico/envenenamiento , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Cohortes , Humanos , Riñón/efectos de los fármacos , Pruebas de Función Renal , MicroARNs/sangre , MicroARNs/orina
18.
DNA Cell Biol ; 39(11): 2005-2016, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32986505

RESUMEN

Background and Aims: Exosomes contain numerous RNAs and transfer them between cells or organs, thereby establishing intercellular or interorgan communication. The roles of mRNAs and long noncoding RNAs (lncRNAs) from umbilical cord blood exosomes in gestational diabetes mellitus (GDM) occurrence and fetus growth remain poorly understood. We aimed to establish the differential mRNA and lncRNA expression profiles in umbilical cord blood exosomes from GDM patients compared with normal controls. Results: Using microarray technology, we identified 84 mRNAs and 256 lncRNAs as differentially expressed in umbilical cord blood exosomes of GDM patients compared with controls. The protein-protein interaction network revealed that the differentially expressed mRNAs were associated with glucagon signaling pathway, an important GDM-related pathway. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses were performed for mRNAs associated with differentially expressed lncRNAs. The results indicated that metabolic process, growth, and development were significantly enriched, which are important in GDM development and fetus growth. Moreover, pathway network was constructed to reveal the key pathways in GDM, such as metabolic pathways and insulin signaling pathway. Further lncRNA/miRNA interaction analysis showed that most of the exosomal lncRNAs harbored miRNA binding sites, and some were associated with GDM. Conclusion: These results showed that exosomal mRNAs and lncRNAs are aberrantly expressed in the umbilical cord blood of GDM patients and play potential roles in GDM development and fetus growth.


Asunto(s)
Diabetes Gestacional/sangre , ARN Largo no Codificante/sangre , ARN Mensajero/sangre , Transcriptoma/genética , Adulto , Diabetes Gestacional/genética , Diabetes Gestacional/patología , Exosomas/genética , Femenino , Sangre Fetal/metabolismo , Humanos , Recién Nacido , Insulina/sangre , MicroARNs/sangre , Análisis por Micromatrices , Embarazo , Transducción de Señal/genética
19.
Proc Natl Acad Sci U S A ; 117(40): 25036-25042, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32943537

RESUMEN

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Detección Precoz del Cáncer , MicroARNs/sangre , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad
20.
J Clin Lab Anal ; 34(10): e23590, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32960473

RESUMEN

INTRODUCTION: The coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which play important roles in regulating gene expression and are also considered as essential modulators during viral infection. The aim of this study was to elucidate the differential expression of miRNAs in COVID-19. METHODS: The total RNA was extracted and purified from the peripheral blood of ten patients with COVID-19 and four healthy donors. The expression levels of various miRNAs were detected by high-throughput sequencing, and correlation analysis was performed on the target genes that are primed by miRNAs. KEY FINDINGS: Compared with the healthy controls, 35 miRNAs were upregulated and 38 miRNAs were downregulated in the human patients with COVID-19. The top 10 genes were listed below: hsa-miR-16-2-3P,hsa-miR-5695,hsa-miR-10399-3P,hsa-miR-6501-5P,hsa-miR-361-3P,hsa-miR-361-3p, hsa-miR-4659a-3p, hsa-miR-142-5p, hsa-miR-4685-3p, hsa-miR-454-5p, and hsa-miR-30c-5p. The 10 genes with the greatest reduction were listed below: hsa-miR-183-5p, hsa-miR-627-5p, hsa-miR-941, hsa-miR-21-5p, hsa-miR-20a-5p, hsa-miR-146b-5p, hsa-miR-454-3p, hsa-miR-18a-5p, hsa-miR-340-5p, and hsa-miR-17-5p. Remarkably, miR-16-2-3p was the most upregulated miRNA, with a 1.6-fold change compared to that of the controls. Moreover, the expression of miR-6501-5p and miR-618 was 1.5-fold higher in the COVID-19 patients than in the healthy donors. Meanwhile, miR-627-5p was the most downregulated miRNA, with a 2.3-fold change compared to that of the controls. The expression of other miRNAs (miR-183-5p, miR-627-5p, and miR-144-3p) was reduced by more than 1.3-fold compared to that of the healthy donors. Cluster analysis revealed that all of the differentially expressed miRNA target genes were clustered by their regulation of cellular components, molecular functions, and biological processes. Importantly, peptidases, protein kinases, and the ubiquitin system were shown to be the highest enrichment categories by enrichment analysis. CONCLUSIONS: The differential miRNA expression found in COVID-19 patients may regulate the immune responses and viral replication during viral infection.


Asunto(s)
Infecciones por Coronavirus , MicroARNs , Pandemias , Neumonía Viral , Adulto , Betacoronavirus , Biología Computacional , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Femenino , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , MicroARNs/sangre , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Neumonía Viral/sangre , Neumonía Viral/epidemiología , Análisis de Secuencia de ARN , Adulto Joven
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