Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 804
Filtrar
1.
Biomed Pharmacother ; 128: 110316, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32505821

RESUMO

BACKGROUND: Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been clinically used as an anti-SARS-CoV-2 infectory agent in China. PDL might also have therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified. METHODS: We used network pharmacology analysis and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform. RESULTS: PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It might inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C motif chemokine ligand 5 (CCL5), transforming growth factor-ß1 (TGFß1), and other proteins. PDL might moderate the immune system to shorten the course of the disease, delay disease progression, and reduce the mortality rate. CONCLUSION: PDL might have a therapeutic effect on COVID-19 through three aspects, including the moderate immune system, anti-inflammation, and anti-virus entry into cells.


Assuntos
Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus , Síndrome da Liberação de Citocina , Medicamentos de Ervas Chinesas/farmacologia , Pandemias , Pneumonia Viral , Internalização do Vírus/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Inflamatórios/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Fatores Imunológicos/farmacologia , Interferon gama/imunologia , Interleucinas/imunologia , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Mapas de Interação de Proteínas , Fator de Crescimento Transformador beta/imunologia
2.
Sensors (Basel) ; 20(11)2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32498374

RESUMO

This study proposes a novel multi-network architecture consisting of a multi-scale convolution neural network (MSCNN) with fully connected graph convolution network (GCN), named MSCNN-GCN, for the detection of musculoskeletal abnormalities via musculoskeletal radiographs. To obtain both detailed and contextual information for a better description of the characteristics of the radiographs, the designed MSCNN contains three subnetwork sequences (three different scales). It maintains high resolution in each sub-network, while fusing features with different resolutions. A GCN structure was employed to demonstrate global structure information of the images. Furthermore, both the outputs of MSCNN and GCN were fused through the concat of the two feature vectors from them, thus making the novel framework more discriminative. The effectiveness of this model was verified by comparing the performance of radiologists and three popular CNN models (DenseNet169, CapsNet, and MSCNN) with three evaluation metrics (Accuracy, F1 score, and Kappa score) using the MURA dataset (a large dataset of bone X-rays). Experimental results showed that the proposed framework not only reached the highest accuracy, but also demonstrated top scores on both F1 metric and kappa metric. This indicates that the proposed model achieves high accuracy and strong robustness in musculoskeletal radiographs, which presents strong potential for a feasible scheme with intelligent medical cases.

3.
Gut Microbes ; 11(5): 1450-1474, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32515683

RESUMO

Aging is usually characterized with inflammation and disordered bile acids (BAs) homeostasis, as well as gut dysbiosis. The pathophysiological changes during aging are also sexual specific. However, it remains unclear about the modulating process among gut microbiota, BA metabolism, and inflammation during aging. In this study, we established a direct link between gut microbiota and BA profile changes in the liver, serum, and four intestinal segments of both sexes during aging and gut microbiota remodeling by co-housing old mice with young ones. We found aging reduced Actinobacteria in male mice but increased Firmicutes in female mice. Among the top 10 altered genera with aging, 4 genera changed oppositely between male and female mice, and most of the changes were reversed by co-housing in both sexes. Gut microbiota remodeling by co-housing partly rescued the systemically dysregulated BA homeostasis induced by aging in a sex- and tissue-specific manner. Aging had greater impacts on hepatic BA profile in females, but intestinal BA profile in males. In addition, aging increased hepatic and colonic deoxycholic acid in male mice, but reduced them in females. Moreover, muricholic acids shifted markedly in the intestine, especially in old male mice, and partially reversed by co-housing. Notably, the ratios of primary to secondary BAs in the liver, serum, and all four intestinal segments were increased in old mice and reduced by co-housing in both sexes. Together, the presented data revealed that sex divergent changes of gut microbiota and BA profile in multiple body compartments during aging and gut microbiota remodeling, highlighting the sex-specific prevention and treatment of aging-related disorders by targeting gut microbiota-regulated BA metabolism should particularly be given more attention.

4.
Org Lett ; 22(12): 4627-4632, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32511927

RESUMO

The biosynthetic gene cluster (BGC) for polyether antibiotic K-41A was identified from marine-derived Streptomyces sp. SCSIO 01680 and subjected to combinatorial biosynthetic study. Bioinformatics analyses, gene disruption, and metabolomics analyses afforded eight new derivatives and one known polyether, showcasing five region-specific methyltransferases Pak13, Pak15, Pak20, Pak31, and Pak38 and their respective modification loci. Moreover, bioassays revealed that two disaccharide-bearing polyethers, K-41B and K-41Bm, display enhanced anti-HIV and potent antibacterial activities.

5.
Clin Transl Med ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32508046

RESUMO

The deregulated DLX gene family members DLX1/2/3/4/5/6 (DLXs) caused by DNA methylation has been demonstrated in various cancers with therapeutic target value. However, the potential role of DLXs methylation in myeloid neoplasms such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remains to be elucidated. Clinical significance of DLXs methylation/expression was analyzed in patient with AML and MDS. The functional roles of DLXs were determined in vitro. In the identification stage, we found that lower DLX5 expression was correlated with prognosis in AML among all DLXs analyzed by The Cancer Genome Atlas datasets. In the validation stage, we revealed that reduced DLX5 expression was frequently occurred, and was also correlated with promoter hypermethylation in AML evaluated by targeted bisulfite sequencing. Epigenetic studies also showed that DLX5 promoter DNA methylation was associated with its expression. By quantitative polymerase chain reaction, we also validated that DLX5 hypermethylation was frequent event in both AML and MDS, and also correlated with MDS transformation to leukemia. Moreover, DLX5 hypermethylation was associated with lower rate of complete remission and shorter time of leukemia-free/overall survival, and was also confirmed by Logistic/Cox regression analysis. Functional studies revealed the antiproliferative and pro-apoptotic effects of DLX5 in MDS-derived AML cell-line SKM-1. Finally, bioinformatics analysis demonstrated that DLX5 functioned in leukemogenesis may be through the association with PI3K/Akt signaling pathway. Collectively, our findings demonstrated that DLX5 methylation, negatively correlated DLX5 expression, was a potential prognostic and predictive indicator in patients with AML and MDS, which could also act as an epigenetic driver in myeloid neoplasms.

6.
Arch Oral Biol ; 117: 104773, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32512259

RESUMO

OBJECTIVE: The aim of this study was to analyze the occurrence and variations in C-shaped canals in ancient Chinese teeth and compare the differences of these features between ancient and age-matched modern populations. DESIGN: Approximately 5000-year-old craniofacial bone remains were collected from the fossils of 38 individuals (total: 68 mandibular second molars) excavated from the Jiaojia site. The control group comprised of an equal number of randomly selected modern samples. We used cone-beam computed tomography to scan the mandible along the apex-crown axis and analyzed the canal morphology, based on Fan's categorization criterion, at 2 mm, 5 mm, and 8 mm to the apical level. Grooves on the lingual and buccal sides were also recorded. RESULTS: The proportion of C-shaped roots among ancient samples on the left and right sides were 48.57 % (17/35 teeth) and 54.55 % (18/33 teeth), respectively, and 51.47 % (35/68 teeth) in the total sample. Conversely, in the control group, 44.12 % (15/34) and 38.24 % (13/34) occurred on the left and right sides, respectively, and 41.18 % (28/68) in the total sample. Among the C-shaped canals from the Jiaojia site samples, the classification type changed between two adjacent levels in 84.31 % of samples. Approximately 35 (51.5 %) teeth had a fused root, 20 (29.41 %) had one shallow buccal and one deep lingual groove. The occurrence of C-shape variation was not significantly correlated with time (p>0.05). CONCLUSIONS: This study identified a high rate of C-shaped root canals among individuals of Jiaojia who lived approximately 5000 years ago.

7.
Steroids ; 161: 108681, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32590045

RESUMO

Two novel steroidal derivatives, erectsterates A (1) and B (2), a pair of epimers at C-10, were isolated from the South China Sea soft coral Sinularia erecta. Their structures were established by extensive spectroscopic analysis and deduction from biosynthesis route. Compounds 1 and 2 are rare steroids with a highly degradation in ring B and an ester linkage between A and C/D rings, similar with the known compounds chaxines B (3) and D from an edible mushroom Agrocybe chaxingu. To the best of our knowledge, this is the first report of such kind of steroid from soft coral. And a different biosynthetic route from the reported approach of chaxines was proposed in this paper. Interestingly, the ring C of 1 and 2 was formally oxidized by Baeyer-Villiger reaction to provide an unprecedented seven-membered lactone moiety in ring C of steroid. The in vitro anti-proliferative activities of 2 were evaluated against A549, HT-29, SNU-398 and Capan-1 cell lines. The results indicated that it showed weak cytotoxicity against the tested four cell lines.

8.
Mol Neurobiol ; 57(7): 3195-3205, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32504418

RESUMO

Alcoholism is a chronic relapsing disorder defined by loss of control over excessive consumption of ethanol despite damaging effects on the liver and brain. We previously showed that the overexpression in mice of Dyrk1A (TgDyrk1A, for dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A) reduces the severity of alcohol mediated liver injury. Ethanol consumption has also been associated with increased brain glutamate concentration that led to therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Interestingly, mice overexpressing Dyrk1A (TgDyrk1A mice) present a reduction of glutamatergic brain transmission, which we propose could be protective against alcohol intake. To answer this question, we investigated the ethanol preference in TgDyrk1A mice using a two-bottle choice paradigm. TgDyrk1A mice showed a non-significant decrease of voluntary ethanol intake and ethanol preference compared with wild-type mice. At the peripheral level, mice overexpressing Dyrk1A show lower ethanol plasma levels, indicating a faster ethanol metabolism. At the end of the protocol, lasting 21 days, brains were extracted for protein analysis. Ethanol reduced levels of the synaptic protein PSD-95 and increased the glutamate decarboxylase GAD65, specifically in the cortex of TgDyrk1A mice. Our results suggest that overexpression of DYRK1A may cause different ethanol-induced changes in the brain.

9.
Liver Int ; 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32564486

RESUMO

BACKGROUND & AIMS: T-cell receptor (TCR) repertoire is ambiguously changed in chronic hepatitis B (CHB) patients during anti-virus therapy. We tried to assess TCR repertoire dynamics and its clinical significance upon HBeAg seroconversion in CHB patients. METHODS: Twenty CHB patients undergoing 1-year entecavir (ETV) treatment were enrolled, including 10 complete response (CR) vs 10 non-complete response (NCR) patients based on HBeAg seroconversion at week 48. The TCRß complementarity-determining region 3 (CDR3) of peripheral CD4+ and CD8+ T cells at weeks 0, 12 and 48 was analyzed by unbiased high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed. RESULTS: The diversity of TCRß repertoires was decreasing in CR patients but increasing in NCR patients. The distribution pattern of TCR repertoires stratified according to clonotype frequencies changed in the opposite direction between CR and NCR patients. Narrow amounts of newly appearing clonotypes in CR patients experienced a more intensive and robust expansion and this phenomenon could occur as early as week 12 for the CD4+ subset but later at week 48 for the CD8+ subset. There existed some CR-exclusive clonotypes with a relatively low but increasing frequency at week 48. The number of unique TCRß clonotypes was positively correlated with the ALT or HBV DNA level in CR patients but showed no or negative correlation in NCR patients. CONCLUSION: Distinct TCR profiles contribute to predicting HBeAg seroconversion in CHB patients during ETV treatment and certain TCRß CDR3 motif may be utilized for CHB immunotherapy in the future.

10.
J Dig Dis ; 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32537911

RESUMO

The natural history of Crohn's disease (CD) usually begins with primary intestinal inflammation, which progresses gradually to stricturing lesions. Stricture is a complicated, intractable but very common clinical problem in the management of CD. Difficulties remain in treating stricturing CD because of the limited efficacy of drug therapy and relapse of stricturing lesions cannot be completely avoided by surgery. Endoscopic management is a bridging therapy between drug therapy and surgical intervention, mainly including endoscopic balloon dilatation and endoscopic stricturotomy, and has been found to be effective for treating stricturing CD. Its explicit curative effect, less invasiveness and high safety performance make endoscopic management more acceptable by both the physician and patient. Although some patients require repeated endoscopic treatment and ultimately cannot avoid surgery, yet it can significantly delay the time to surgery and improve the quality of life. Physicians carrying out the endoscopic procedure need to be trained for performing this procedure. In this review we summarized the diagnosis and endoscopic treatment of stricturing CD. This article is protected by copyright. All rights reserved.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32424483

RESUMO

PURPOSE: The purpose was to investigate the effects of short acquisition time on the image quality and the lesion detectability of oncological 18F-FDG total-body PET/CT. METHODS: Nineteen oncological patients (6/13 women/men, age 65.6 ± 9.4 years) underwent total-body PET/CT on uEXPLORER scanner using 3D list mode. The administration of 18F-FDG was weight-based (4.4 MBq/kg). The acquisition time was 900 s, and PET data were reconstructed into 900-, 180-, 120-, 60-, 30-, and 18-s duration groups. The subjective PET image quality was scored using a 5-point scale (5, excellent; 1, poor) in 3 perspectives: overall quality, noise, and lesion conspicuity. The objective image quality was evaluated by SUVmax and standard deviation (SD) of the liver, SUVmax of the tumor, and tumor-to-background ratio (TBR). The lesion detectability was the percentage of identifiable lesions in the groups of 180 to 18 s using the group 900 s as reference. RESULTS: Our results showed that sufficient and acceptable subjective image quality could be achieved with 60- and 30-s groups, and good image quality scores were given to 180- and 120-s groups without significant difference. For shortened acquisition time, SD was increased, while SUVmax of tumor and TBR remained unchanged. The lesion detectability was decreased with shorter acquisition time, but the detection performance could be maintained until the 60-s group compared with the 900-s group, although the image quality degraded. CONCLUSION: The total-body PET/CT can significantly shorten the acquisition time with maintained lesion detectability and image quality.

13.
Neurosci Bull ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367252
14.
J Ethnopharmacol ; 259: 113001, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464316

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) is a commercial Chinese medicine included in the Chinese Pharmacopoeia with well-established cardiovascular protect effect in clinic. However, the mechanism of SBP underlying protective effect on cardiovascular disease has not been clearly elucidated yet. AIM OF THE STUDY: We aimed to investigate the underlying protective mechanisms of SBP on an acute myocardial infarction (AMI) rat model by using comprehensive metabolomics. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. After two weeks of treatment with SBP, comprehensive metabolomics and echocardiography index was performed for a therapeutic evaluation. The wiff data were processed using Progenesis QI and metabolites were identified based on the database of HMDB and LIPIDMAPS. Meanwhile, the untargeted metabolomics data from LC-MS combined with correlation analysis to characterize the metabolic alterations. RESULTS: The metabolomics profiles of different groups in different biological samples (heart, serum, urine and feces) were significantly different, in which a total of 217 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism, while SBP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism, butanoate metabolism and glycerophospholipid metabolism. Correlation analysis found that SBP could significantly alter the metabolic activity of six key metabolites (5-hydroxyindoleacetic acid, glycerophosphocholine, PS (20:4/0:0), xanthosine, adenosine and L-phenylalanine) related to AMI. The key role of these metabolites was further validated with correlation analysis with echocardiography indexes. CONCLUSION: This study demonstrated that SBP was effective for protecting cardiac dysfunction by regulating amino acid, lipid and energy metabolisms. The results also suggested that the modulation on gut microbiota might be involved the cardioprotective effect of SBP.

15.
J Transl Med ; 18(1): 212, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460807

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

17.
Sensors (Basel) ; 20(7)2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32235507

RESUMO

Signal drift caused by sensors or environmental changes, which can be regarded as data distribution changes over time, is related to transductive transfer learning, and the data in the target domain is not labeled. We propose a method that learns a subspace with maximum independence of the concentration features (MICF) according to the Hilbert-Schmidt Independence Criterion (HSIC), which reduces the inter-concentration discrepancy of distributions. Then, we use Iterative Fisher Linear Discriminant (IFLD) to extract the signal features by reducing the divergence within classes and increasing the divergence among classes, which helps to prevent inconsistent ratios of different types of samples among the domains. The effectiveness of MICF and IFLD was verified by three sets of experiments using sensors in real world conditions, along with experiments conducted in the authors' laboratory. The proposed method achieved an accuracy of 76.17%, which was better than any of the existing methods that publish their data on a publicly available dataset (the Gas Sensor Drift Dataset). It was found that the MICF-IFLD was simple and effective, reduced interferences, and deftly managed tasks of transfer classification.

18.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1225-1231, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281329

RESUMO

Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to "cytokine storm". "Cytokine storm" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the "cytokine storm". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on "cytokine storm" according to the potential herbs in the "National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)". The results showed that the hit components with the inhibitory effect on AA were magnolignan Ⅰ, lonicerin and physcion-8-O-ß-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.


Assuntos
Ácido Araquidônico/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Betacoronavirus , Humanos , Medicina Tradicional Chinesa , Redes e Vias Metabólicas , Pandemias
19.
Mol Cancer ; 19(1): 80, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345328

RESUMO

Recent studies have reported that COVID-19 patients with lung cancer have a higher risk of severe events than patients without cancer. In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Lung cancer patients in each age stage, subtype, and pathological stage are susceptible to SARS-CoV-2 infection, except for the primitive subtype of LUSC. LUAD patients are more susceptible to SARS-CoV-2 infection than LUSC patients. The findings are unanimous on tissue expression in gene and protein levels.


Assuntos
Adenocarcinoma de Pulmão/complicações , Betacoronavirus , Carcinoma de Células Escamosas/complicações , Infecções por Coronavirus/etiologia , Neoplasias Pulmonares/complicações , Peptidil Dipeptidase A/genética , Pneumonia Viral/etiologia , Serina Endopeptidases/genética , Adenocarcinoma de Pulmão/genética , Animais , Carcinoma de Células Escamosas/genética , Linhagem Celular , Infecções por Coronavirus/genética , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Camundongos , Camundongos Transgênicos , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral/genética , Serina Endopeptidases/biossíntese
20.
Mol Ther ; 28(6): 1479-1493, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32246902

RESUMO

The discovery of long noncoding RNAs (lncRNAs) has increased our understanding of the development and progression of many cancers, but their contributions to non-small cell lung cancer (NSCLC) remain poorly understood. Here, we profiled lncRNA expression in NSCLC and investigated in detail the molecular function of one upregulated lncRNA, LINC01234. LINC01234 was overexpressed in NSCLC compared with normal lung tissue and correlated positively with poor prognosis. Downregulation of LINC01234 impaired cell proliferation in vitro and tumor growth in vivo. RNA pull-down/mass spectrometry experiments showed that LINC01234 interacted with the RNA-binding protein heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), which, in turn, led to the recruitment of DiGeorge syndrome critical region gene 8 (DGCR8), a subunit of the microRNA (miRNA) microprocessor complex. Accordingly, depletion of either LINC01234 or HNRNPA2B1 reduced the processing of several miRNA precursors, including primary microRNA (pri-miR)-106b. miR-106b-5p enhanced NSCLC cell growth by downregulating cryptochrome 2 (CRY2), thereby increasing c-Myc expression. Finally, we found that activated c-Myc binds to the LINC01234 promoter to increase its transcription, creating a c-Myc-LINC01234-HNRNPA2B1-miR-106b-5p-CRY2-c-Myc positive-feedback loop. We identified numerous lncRNAs with dysregulated expression in NSCLC and demonstrated a novel oncogenic axis involving LINC01234, HNRNPA2B1, miR-106b-5p, CRY2, and c-Myc. Components of this axis may be potential novel targets for NSCLC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA