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1.
Medicine (Baltimore) ; 99(33): e21706, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872046

RESUMO

MicroRNAs (miRNAs) have been suggested to act critical roles in the pathophysiology of traumatic osteonecrosis of the femoral head (TONFH). Unfortunately, their roles in the development of TONFH are still ambiguous. The purpose of this study is to identify promising miRNA biomarkers in traumatic osteonecrosis development.We conducted a comprehensive bioinformatics analysis using microarray datasets downloaded from the Gene Expression Omnibus database, and compared the expression of miRNAs in the serum of TONFH patients with controls. Next, we performed target prediction, function enrichment analysis, and protein-protein interaction network analysis based on differentially expressed (DE) miRNAs.We identified 26 DE miRNAs that may contribute to the pathophysiology of TONFH. The miRNAs were linked to ubiquitin proteasome system including conjugating protein ligase activity, ubiquitin-protein ligase activity and ubiquitin mediated proteolysis 5 pathway, and we exposed miR-181a-5p and miR-140-5p as promising biomarkers in TONFH.A predicting model consisting of 5 miRNAs may help discriminating high-risk patients who might develop TONFH after femur neck fracture. Among DE miRNAs, MiR-181a-5p and miR-140-5p may contribute to the development femoral head osteonecrosis after femur neck fracture via ubiquitin proteasome system.


Assuntos
Fraturas do Colo Femoral/genética , Necrose da Cabeça do Fêmur/genética , MicroRNAs/análise , Ubiquitina/genética , Biomarcadores/metabolismo , Biologia Computacional , Feminino , Fraturas do Colo Femoral/cirurgia , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética
2.
Life Sci ; 259: 118174, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745529

RESUMO

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of the reproductive age. PCOS is commonly manifested as ovulatory dysfunction, clinical and biochemical excess androgen level, and polycystic ovaries. Metabolic sequelae associated with PCOS, including insulin resistance (IR), type 2 diabetes (T2DM), obesity and increased cardiometabolic risk. The underlying pathology of PCOS is not fully understood with various genetic and environmental factors have been proposed. MicroRNAs (miRNAs), are endogenously produced, small non-coding, single-stranded RNAs that capable of regulating gene expression at the post-transcriptional level. Altered miRNAs expression has been associated with various disorders, including T2DM, IR, lipid disorder, infertility, atherosclerosis, endometriosis, and cancer. Given that PCOS also present with similar features, there is an increasing interest to investigate the role of miRNAs in the diagnosis and management of PCOS. In recent years, studies have demonstrated that miRNAs are present in various body fluids, including follicular fluid of women with PCOS. Therefore, it may act as a potential biomarker and could serve as a novel therapeutic target for the diagnosis and treatment of PCOS. This review aims to summarise the up to date research on the relation between miRNAs and PCOS and explore its potential role in the diagnosis and the management of PCOS.


Assuntos
Biomarcadores/análise , MicroRNAs/análise , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações
3.
PLoS One ; 15(7): e0236126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667939

RESUMO

Pasteurization of donated human milk preserves it for storage and makes it safe for feeding, but at the expense of its composition, nutritional values and functions. Here, we aimed to investigate the impact of Holder Pasteurization (HoP) and High Pressure Processing (HPP) methods on miRNA in human milk and to evaluate impact of these changes on miRNA functions. Milk samples obtained from women in 50th day of lactation (n = 3) were subjected either to HoP, HPP or remained unpasteurized as a control. Subsequently, miRNA was isolated from whole material and exosomal fraction and sequenced with Illumina NextSeq 500. Sequencing data were processed, read counts were mapped to miRNA and analyzed both quantitatively with DESeq2 and functionally with DIANA mirPath v.3. While HPP caused statistically insignificant decrease in number of miRNA reads compared to unprocessed material, HoP led to 82-fold decrease in whole material (p = 0.0288) and 302-fold decrease in exosomes (p = 0.0021) not leaving enough reads for further analysis. Changes in composition of miRNA fraction before and after HPP indicated uneven stability of individual miRNAs under high pressure conditions, with miR-30d-5p identified as relatively stable and miR-29 family as sensitive to HPP. Interestingly, about 2/3 of unprocessed milk miRNA content consists of only 10 distinct miRNAs with miR-148a-3p at the top. Functional analysis of most abundant human milk miRNAs showed their involvement in signaling pathways, cell communication, proliferation and metabolism that are obviously important in rapidly growing infants. Functions of miRNAs which suffered the greatest depletion during HPP were similar to roles of the majority of unprocessed human milk's miRNA, which indicates that those functions may be weakened although not completely lost. Our findings indicate that HPP is less detrimental to human milk miRNAs than HoP and should be considered in further research on recommended processing procedures for human milk banks.


Assuntos
Exossomos/genética , MicroRNAs/análise , MicroRNAs/genética , Pasteurização/métodos , Pressão , Manejo de Espécimes/métodos , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Leite Humano , Adulto Jovem
4.
Med Hypotheses ; 143: 110124, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721813

RESUMO

Utilising biomarkers for COVID-19 diagnosis, prediction of treatment response and overall prognostication have been investigated recently. However, these ventures have only considered the use of blood-based molecular markers. Saliva is another biofluid that warrants being applied in similar fashion with major advantages that centres on its non-invasive and repeatable collection as well as cost-efficiency. To this end, this article presents a hypothesis for the sources of biomarkers useful clinically for COVID-19 disease outcome estimation and identify the likely implications of their detection in saliva.


Assuntos
Betacoronavirus , Biomarcadores/análise , Infecções por Coronavirus/metabolismo , Modelos Imunológicos , Pandemias , Pneumonia Viral/metabolismo , Saliva/química , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Citocinas/análise , Testes Diagnósticos de Rotina , Vesículas Extracelulares , Líquido do Sulco Gengival/química , Humanos , MicroRNAs/análise , Doenças da Boca/complicações , Doenças da Boca/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Saliva/imunologia , Saliva/virologia , Glândulas Salivares/metabolismo , Glândulas Salivares/virologia , Proteínas e Peptídeos Salivares/análise
5.
Med Hypotheses ; 143: 110124, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: covidwho-662554

RESUMO

Utilising biomarkers for COVID-19 diagnosis, prediction of treatment response and overall prognostication have been investigated recently. However, these ventures have only considered the use of blood-based molecular markers. Saliva is another biofluid that warrants being applied in similar fashion with major advantages that centres on its non-invasive and repeatable collection as well as cost-efficiency. To this end, this article presents a hypothesis for the sources of biomarkers useful clinically for COVID-19 disease outcome estimation and identify the likely implications of their detection in saliva.


Assuntos
Betacoronavirus , Biomarcadores/análise , Infecções por Coronavirus/metabolismo , Modelos Imunológicos , Pandemias , Pneumonia Viral/metabolismo , Saliva/química , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Citocinas/análise , Testes Diagnósticos de Rotina , Vesículas Extracelulares , Líquido do Sulco Gengival/química , Humanos , MicroRNAs/análise , Doenças da Boca/complicações , Doenças da Boca/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Saliva/imunologia , Saliva/virologia , Glândulas Salivares/metabolismo , Glândulas Salivares/virologia , Proteínas e Peptídeos Salivares/análise
6.
Acta Cir Bras ; 35(3): e202000305, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520081

RESUMO

PURPOSE: To evaluate the effect of chronic alcoholism on morphometry and apoptosis mechanism and correlate with miRNA-21 expression in the corpus cavernosum of rats. METHODS: Twenty-four rats were divided into two experimental groups: Control (C) and Alcoholic group (A). After two weeks of an adaptive phase, rats from group A received only ethanol solution (20%) during 7 weeks. The morphometric and caspase-3 immunohistochemistry analysis were performed in the corpus cavernosum. The miRNA-21 expression was analyzed in blood and cavernous tissue. RESULTS: Chronic ethanol consumption decreased cavernosal smooth muscle area of alcoholic rats. The protein expression of caspase 3 in the corpus cavernosum was higher in A compared to the C group. There was no difference in the expression of miRNA-21 in serum and cavernous tissue between the groups. CONCLUSION: Chronic ethanol consumption reduced smooth muscle area and increased caspase 3 in the corpus cavernosum of rats, without altered serum and cavernosal miR-21 gene expression.


Assuntos
Alcoolismo/complicações , Apoptose/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/patologia , Animais , Caspase 3/análise , Modelos Animais de Doenças , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/patologia , Expressão Gênica , Imuno-Histoquímica , Masculino , MicroRNAs/análise , Músculo Liso/efeitos dos fármacos , Ratos Wistar , Valores de Referência
7.
Medicine (Baltimore) ; 99(23): e20508, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501997

RESUMO

We conducted a study to evaluate the prognostic and diagnostic values of microRNA-10b (miR-10b) in gastric cancer (GC) based on meta-analysis and TCGA database. Relevant studies were searched in English and Chinese database and meta-analysis was conducted on Stata 12.0. The expression value of miR-10b and clinical parameters of GC patients were downloaded from TCGA database, and relevant analyses were conducted on SPSS. High expression of miR-10b was linked with unfavorable overall survival (OS) in GC (HR = 1.572, 95% CI: 1.240-1.992, P < .001). However, the meta-analysis was significant for patients in early stage, but not for patients in advanced stage. The expression of miR-10b-3p was significantly lower in cancer tissue compared with adjacent tissue (P < .001). Meanwhile, the area under the ROC curve (AUC) value was 0.652 (0.562-0.742), P = .001. Disease-free survival analysis showed increasing miR-10b-5p was correlated with worse survival outcome (HR = 2.366, 95% CI: 1.414-3.959, P = .001). In conclusion, miR-10b acts as a tumor suppressor with prognostic and diagnostic values for GC.


Assuntos
MicroRNAs/análise , Prognóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Humanos , MicroRNAs/sangue , Modelos de Riscos Proporcionais , Curva ROC , Neoplasias Gástricas/epidemiologia
8.
PLoS One ; 15(4): e0232351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353026

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by major social, communication and behavioural challenges. The cause of ASD is still unclear and it is assumed that environmental, genetic and epigenetic factors influence the risk of ASD occurrence. MicroRNAs (miRNAs) are short 21-25 nucleotide long RNA molecules which post-transcriptionally regulate gene expression. MiRNAs play an important role in central nervous system development; therefore, dysregulation of miRNAs is connected to changes in behaviour and cognition observed in many disorders including ASD. Based on previously published work, on diagnosing ASD using miRNAs, we hypothesized that miRNAs can be used as biomarkers in children with suspected developmental disorders (DD) including ASD within Bosnian-Herzegovinian (B&H) population. 14 selected miRNAs were tested on saliva of children with suspected developmental disorders including ASD. The method of choice was qRT-PCR as a relatively cheap method available in most diagnostic laboratories in low to mid-income countries (LMIC). Out of 14 analysed miRNAs, 6 were differentially expressed between typically developing children and children with some type of developmental disorder including autism spectrum disorder. Using the most optimal logistic regression, we were able to distinguish between ASD and typically developing (TD) children. We have found 5 miRNAs as potential biomarkers. From those, 3 were differentially expressed within the ASD cohort. All 5 miRNAs had shown good chi-square statistics within the logistic regression performed on all 14 analysed miRNAs. The accuracy of 5-miRNAs model training set was 90.2%, while the validation set had a 90% accuracy. This study has shown that miRNAs may be considered as biomarkers for ASD detection and may be used to identify children with ASD along with standard developmental screening tests. By combining these methods we may be able to reach a reliable and accessible diagnostic model for children with ASD in LMIC such as B&H.


Assuntos
Transtorno do Espectro Autista/genética , MicroRNAs/genética , Saliva/metabolismo , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/metabolismo , Biomarcadores/análise , Bósnia e Herzegóvina , Criança , Pré-Escolar , Feminino , Humanos , Masculino , MicroRNAs/análise , Saliva/química
9.
J Cancer Res Clin Oncol ; 146(8): 1941-1951, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447486

RESUMO

PURPOSE: Currently, the routine screening program has insufficient capacity for the early diagnosis of lung cancer. Therefore, a type of chitosan-molecular beacon (CS-MB) probe was developed to recognize the miR-155-5p and image the lung cancer cells for the early diagnosis. METHODS: Based on the molecular beacon (MB) technology and nanotechnology, the CS-MB probe was synthesized self-assembly. There are four types of cells-three kinds of animal models and one type of histopathological sections of human lung cancer were utilized as models, including A549, SPC-A1, H446 lung cancer cells, tumor-initiating cells (TICs), subcutaneous and lung xenografts mice, and lox-stop-lox(LSL) K-ras G12D transgenic mice. The transgenic mice dynamically displayed the process from normal lung tissues to atypical hyperplasia, adenoma, carcinoma in situ, and adenocarcinoma. The different miR-155-5p expression levels in these cells and models were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The CS-MB probe was used to recognize the miR-155-5p and image the lung cancer cells by confocal microscopy in vitro and by living imaging system in vivo. RESULTS: The CS-MB probe could be used to recognize the miR-155-5p and image the lung cancer cells significantly in these cells and models. The fluorescence intensity trends detected by the CS-MB probe were similar to the expression levels trends of miR-155 tested by qRT-PCR. Moreover, the fluorescence intensity showed an increasing trend with the tumor progression in the transgenic mice model, and the occurrence and development of lung cancer were dynamically monitored by the differen fluorescence intensity. In addition, the miR-155-5p in human lung cancer tissues could be detected by the miR-155-5p MB. CONCLUSION: Both in vivo and in vitro experiments demonstrated that the CS-MB probe could be utilized to recognize the miR-155-5p and image the lung cancer cells. It provided a novel experimental and theoretical basis for the early diagnosis of the disease. Also, the histopathological sections of human lung cancer research laid the foundation for subsequent preclinical studies. In addition, different MBs could be designed to detect other miRNAs for the early diagnosis of other tumors.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , MicroRNAs/análise , Células A549 , Animais , Quitosana/química , Detecção Precoce de Câncer/métodos , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Camundongos Transgênicos , MicroRNAs/biossíntese , MicroRNAs/genética , Imagem Molecular/métodos , Sondas Moleculares/química , Nanotecnologia
10.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276343

RESUMO

MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.


Assuntos
Biomarcadores Tumorais/análise , MicroRNAs/metabolismo , Neoplasias/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Humanos , MicroRNAs/análise , MicroRNAs/genética , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Prognóstico
11.
Medicine (Baltimore) ; 99(17): e19693, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332611

RESUMO

BACKGROUND: microRNAs have drawn more attention due to their function on the inflammatory process. The association between microRNA-21 (miR-21) expression and risk of inflammatory bowel diseases (IBD) remain inconclusive. This study was aimed to acquire a more exact estimation of this relationship. METHODS: Relevant studies were identified through searching PubMed, Embase, Wanfang, and China National Knowledge Infrastructure database. Pooled standardized mean difference and 95% confidence intervals were calculated using a random-effect model. Publication bias test, sensitivity analysis and subgroup analysis were carried out. RESULTS: A total of 20 relevant articles comprising 540 patients with ulcerative colitis (UC), 459 patients with Crohn disease (CD) and 511 non-IBD controls were included in this analysis. The expression of miR-21 was significantly increased in colon tissue of both UC and CD patients compared with non-IBD controls. However, there were no significant differences between patients with UC and CD. Moreover, increased miR-21 expression was associated with disease activity status in UC patients, but not in CD patients. CONCLUSIONS: This meta-analysis demonstrates that the higher miR-21 expression in colon tissue is positively associated with the development of UC and CD, and miR-21 might serve as a disease marker of IBD.


Assuntos
Protocolos Clínicos , Doenças Inflamatórias Intestinais/genética , MicroRNAs/genética , Humanos , Doenças Inflamatórias Intestinais/sangue , Metanálise como Assunto , MicroRNAs/análise , MicroRNAs/sangue , Literatura de Revisão como Assunto
12.
Nucleic Acids Res ; 48(10): e60, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32347938

RESUMO

The construction of robust, modular and compact DNA machinery facilitates us to build more intelligent and ingenious sensing strategies in complex biological systems. However, the performance of conventional DNA amplifiers is always impeded by their limited in-depth amplifications and miscellaneously enzymatic requirements. Here, a proteinase-free reciprocal DNA replication machinery is developed by exploiting the synergistic cross-activation between hybridization chain reaction (HCR) and DNAzyme. The DNAzyme provides an efficient way to simplify the sophisticated design of HCR machinery and simultaneously to promote the amplification capacity. And the HCR-assembled tandem DNAzyme nanowires produce numerous new triggers for reversely stimulating HCR amplifier as systematically explored by experiments and computer-aided simulations. The reciprocal amplifier can be executed as a versatile and powerful sensing platform for analyzing miRNA in living cells and even in mice, originating from the inherent reaction accelerations and multiple-guaranteed recognitions. The reciprocal catalytic DNA machine holds great potential in clinical diagnosis and assessment.


Assuntos
MicroRNAs/análise , Técnicas de Amplificação de Ácido Nucleico/métodos , Animais , Linhagem Celular , Replicação do DNA , DNA Catalítico , Transferência Ressonante de Energia de Fluorescência , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal , Nanofios
13.
PLoS One ; 15(4): e0229976, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275679

RESUMO

Small extracellular vesicles (sEV) are nano-sized (40-150 nm), membrane-encapsulated vesicles that are released by essentially all cells into the extracellular space and function as intercellular signaling vectors through the horizontal transfer of biologic molecules, including microRNA (miRNA) and other small non-coding RNA (ncRNA), that can alter the phenotype of recipient cells. sEV are present in essentially all extracellular biofluids, including serum, urine and saliva, and offer a new avenue for discovery and development of novel biomarkers of various disease states and exposures. The objective of this study was to systematically interrogate similarities and differences between sEV ncRNA derived from saliva, serum and urine, as well as cell-free small ncRNA (cf-ncRNA) from serum. Saliva, urine and serum were concomitantly collected from 4 healthy donors to mitigate potential bias that can stem from interpersonal and temporal variability. sEV were isolated from each respective biofluid, along with cf-RNA from serum. sEV were isolated from the respective biofluids via differential ultracentrifugation with a 30% sucrose cushion to minimize protein contamination. Small RNA-sequencing was performed on each sample, and cluster analysis was performed based on ncRNA profiles. While some similarities existed in terms of sEV ncRNA cargo across biofluids, there are also notable differences in ncRNA class and ncRNA secretion, with sEV in each biofluid bearing a unique ncRNA profile, including major differences in composition by ncRNA class. We conclude that sEV ncRNA cargo varies according to biofluid, so thus should be carefully selected and interpreted when designing or contrasting translational or epidemiological studies.


Assuntos
Biomarcadores/análise , Vesículas Extracelulares/metabolismo , MicroRNAs/análise , Pequeno RNA não Traduzido/análise , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Líquidos Corporais/metabolismo , Testes Diagnósticos de Rotina/métodos , Feminino , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/urina , Pessoa de Meia-Idade , Pequeno RNA não Traduzido/sangue , Pequeno RNA não Traduzido/urina , Saliva/metabolismo , Análise de Sequência de RNA , Ultracentrifugação
14.
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
15.
PLoS Comput Biol ; 16(4): e1007851, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32324747

RESUMO

Until now, existing methods for identifying lncRNA related miRNA sponge modules mainly rely on lncRNA related miRNA sponge interaction networks, which may not provide a full picture of miRNA sponging activities in biological conditions. Hence there is a strong need of new computational methods to identify lncRNA related miRNA sponge modules. In this work, we propose a framework, LMSM, to identify LncRNA related MiRNA Sponge Modules from heterogeneous data. To understand the miRNA sponging activities in biological conditions, LMSM uses gene expression data to evaluate the influence of the shared miRNAs on the clustered sponge lncRNAs and mRNAs. We have applied LMSM to the human breast cancer (BRCA) dataset from The Cancer Genome Atlas (TCGA). As a result, we have found that the majority of LMSM modules are significantly implicated in BRCA and most of them are BRCA subtype-specific. Most of the mediating miRNAs act as crosslinks across different LMSM modules, and all of LMSM modules are statistically significant. Multi-label classification analysis shows that the performance of LMSM modules is significantly higher than baseline's performance, indicating the biological meanings of LMSM modules in classifying BRCA subtypes. The consistent results suggest that LMSM is robust in identifying lncRNA related miRNA sponge modules. Moreover, LMSM can be used to predict miRNA targets. Finally, LMSM outperforms a graph clustering-based strategy in identifying BRCA-related modules. Altogether, our study shows that LMSM is a promising method to investigate modular regulatory mechanism of sponge lncRNAs from heterogeneous data.


Assuntos
Neoplasias da Mama , Biologia Computacional/métodos , MicroRNAs/genética , RNA Longo não Codificante/genética , Algoritmos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Análise por Conglomerados , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Humanos , MicroRNAs/análise , MicroRNAs/metabolismo , RNA Longo não Codificante/análise , RNA Longo não Codificante/metabolismo
16.
Respir Investig ; 58(4): 232-238, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305227

RESUMO

Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology. Diagnosis of sarcoidosis is made by correlating clinical and radiological features along with the histopathological demonstration of non-necrotizing granulomas in tissue samples. Diagnosis is often challenging as the clinical profile may mimic other granulomatous disorders, including infections, inflammatory diseases, and lymphoid malignancies. Differentiation from tuberculosis is especially crucial in endemic regions where exclusion of mediastinal tuberculosis is necessary before any immunosuppressant treatment can be initiated for symptomatic sarcoidosis. Identification of biomarkers, which can aid in diagnosis as well as prognosis, can be helpful in clinical decision making. MicroRNAs are small non-coding regulatory RNAs that serve as post-transcriptional regulators of gene expression and have been studied as emerging biomarkers in many other respiratory diseases, including lung cancer, asthma, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In the context of sarcoidosis, miRNA expression has been studied in the lungs, lymph nodes, bronchoalveolar lavage fluid, and peripheral blood mononuclear cells. A comprehensive search of the PubMed database was performed by two authors independently, and relevant studies were retrieved for review. This systematic review summarizes the current information on miRNAs in sarcoidosis, the biological mechanisms involved in CD4+ T-helper 1 and macrophage polarization, and the use of exhaled breath condensate as an alternative, noninvasive and potential source of miRNAs.


Assuntos
MicroRNAs/análise , Sarcoidose Pulmonar/diagnóstico por imagem , Biomarcadores/análise , Testes Respiratórios , Líquido da Lavagem Broncoalveolar , Linfócitos T CD4-Positivos , Diagnóstico Diferencial , Expressão Gênica , Humanos , Leucócitos Mononucleares , Pulmão/metabolismo , Linfonodos/metabolismo , Macrófagos , MicroRNAs/genética , Linfócitos T Auxiliares-Indutores
17.
Bratisl Lek Listy ; 121(2): 159-163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115971

RESUMO

AIM: In 95 % of Chronic myeloid leukemia (CML) patients, chromosomal translocation resulting in the formation of the Philadelphia (Ph) chromosome (t:9;22) is observed, which in turn leads to the formation of the BCR-ABL fusion gene. MicroRNAs (miRNAs) are a group of small and non-coding RNAs modulating gene expression via binding to the target mRNAs. We aimed to characterize the expression profiles of various miRNAs in different stages of Ph(+) CML patients. METHODS: This case-controlled study was conducted in 75 CML patients and 25 healthy controls. The subjects were categorized into 4 groups; newly diagnosed patients, treatment-response patients, treatment-failure patients, and healthy controls. Expressions of miRNAs was analyzed by RT-PCR. RESULTS: miR-150 expression was downregulated in the treatment failure patients compared to the control group (p = 0.003212) while miRNA 148b expression up-regulated in the treatment failure patients than the control group (p = 0.038016). miR-10a expression was up-regulated in newly diagnosed and treatment response patients compared to control group (p = 0.003934, p = 0.000292, respectively). It was found that miR-10a expression increased 11.17- fold in newly diagnosed patients and 9.82-fold in treatment response patients than in the control group. CONCLUSION: Our data suggest that expression profiles of miR-10a, miR-150, and miRNA 148b were correlated as biomarker and therapeutic tool in Turkish patients with CML (Tab. 2, Fig. 1, Ref. 30).


Assuntos
Biomarcadores , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , Biomarcadores/metabolismo , Estudos de Casos e Controles , Proteínas de Fusão bcr-abl , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , MicroRNAs/análise , RNA Mensageiro , Transcriptoma
18.
Nat Commun ; 11(1): 1543, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32210235

RESUMO

Field-effect transistor (FET)-based biosensors allow label-free detection of biomolecules by measuring their intrinsic charges. The detection limit of these sensors is determined by the Debye screening of the charges from counter ions in solutions. Here, we use FETs with a deformed monolayer graphene channel for the detection of nucleic acids. These devices with even millimeter scale channels show an ultra-high sensitivity detection in buffer and human serum sample down to 600 zM and 20 aM, respectively, which are ∼18 and ∼600 nucleic acid molecules. Computational simulations reveal that the nanoscale deformations can form 'electrical hot spots' in the sensing channel which reduce the charge screening at the concave regions. Moreover, the deformed graphene could exhibit a band-gap, allowing an exponential change in the source-drain current from small numbers of charges. Collectively, these phenomena allow for ultrasensitive electronic biomolecular detection in millimeter scale structures.


Assuntos
Técnicas Biossensoriais/instrumentação , Sondas de DNA/análise , DNA de Cadeia Simples/análise , Grafite/química , MicroRNAs/análise , Sondas de DNA/química , DNA de Cadeia Simples/química , Estudos de Viabilidade , Humanos , Íons , Limite de Detecção , MicroRNAs/química , Simulação de Dinâmica Molecular , Sensibilidade e Especificidade , Transistores Eletrônicos
19.
Jpn J Clin Oncol ; 50(6): 671-678, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32129446

RESUMO

OBJECTIVE: Multidrug resistance and consequent relapse are two major obstacles for treating children with acute lymphoblastic leukemia, the most frequent childhood malignancy. MicroRNAs have potential regulatory roles in response to chemotherapy. The goal of this study was to determine the microRNA that may have effects on the expression level of brain and acute lymphoblastic leukemia (BAALC) and to investigate the in vitro and ex vivo association between their expression levels. METHODS: In silico tools were utilized to determine a putative miRNA targeting BALLC. Quantitative real-time polymerase chain reaction was used to investigate expression levels of BAALC and its predicted microRNA, miR-326, in bone marrow samples of 30 children with acute lymphoblastic leukemia and 13 controls, in addition to the resistant and parental CCRF-CEM cell lines. To assess the status of response to therapy, minimal residual disease was measured using single-strand conformation polymorphism. RESULTS: MiR-326 was selected due to the strong possibility of its interaction with BAALC according to the obtained in silico results. Statistical analysis showed a significant downregulation of miR-326 and overexpression of BALLC in drug-resistant acute lymphoblastic leukemia cell line and patients compared with the parental cell line and drug-sensitive patients, respectively (P = 0.015, 0.005, 0.0484 and 0.0005, respectively). The expression profiles of miR-326 and BAALC were inversely correlated (P = 0.028). CONCLUSIONS: The results introduced the inversely combined expression levels of miR-326 and BAALC as a novel, independent prognostic biomarker for pediatric acute lymphoblastic leukemia (P = 0.007). Moreover, bioinformatics data showed a possible regulatory role for miR-326 on BAALC mRNA, which may possibly contribute to the development of drug resistance in patients with childhood acute lymphoblastic leukemia.


Assuntos
Biomarcadores/análise , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Medula Óssea/metabolismo , Linhagem Celular Tumoral , Criança , Pré-Escolar , Simulação por Computador , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , MicroRNAs/análise , MicroRNAs/metabolismo , Proteínas de Neoplasias/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
20.
Res Vet Sci ; 130: 52-58, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32145457

RESUMO

The miRNA gene in DNA is first transcribed to Pri-miRNA, and then processed to Pre-miRNA, a stem-loop RNA segment (precursor) and further to miRNA which binds to mRNA by Dicer protein complex. It was confirmed that goat miR-204 could regulate the expressions of Sirt1 and the SSCs' (Spermatogonial Stem Cells) important genes Oct4 and Plzf, and inhibit the proliferation of dairy goat SSCs in vitro in our previous work. So, the research in vivo was needed next. In this study, the recombinant lentivirus vector pCDH-CMV-mir204-EF1-GreenPuro containing a goat chi-pri-mir-204 gene DNA segment was structured, and transfected into 293 T cells for packaged lentivirus, which then were injected into mouse seminiferous tubules. After 7 days, the goat miR-204 and the related genes such as Sirt1 and Plzf were detected in the mouse testis. This work laid a good foundation for further study of miR-204 biological function in vivo.


Assuntos
Cabras/genética , MicroRNAs/análise , Testículo/metabolismo , Animais , Vetores Genéticos , Cabras/metabolismo , Lentivirus , Masculino , Análise de Sequência de RNA/veterinária
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