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1.
Front Cell Dev Biol ; 9: 705962, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422827

RESUMO

Aberrant regulation of m6A mRNA modification can lead to changes in gene expression, thus contributing to tumorigenesis in several types of solid tumors. In this study, by integrating analyses of m6A methylation and mRNA expression, we identified 84 m6A-regulated mRNAs in lung adenocarcinoma (LUAD). Although the m6A methylation levels of total RNA in LUAD patient tumor tissue were reduced, the majority (75.2%) of m6A-regulated mRNAs were hypermethylated. The m6A-hypermethylated mRNAs were mainly enriched in terms related to transcription factor activity. We established a 10-m6A-regulated-mRNA signature score system through least absolute shrinkage and selection operator Cox regression analysis, with its predictive value validated by Kaplan-Meier curve and time-dependent receiver operating characteristic curves. RFXAP and KHDRBS2 from the signature also exhibited an independent prognostic value. The co-expression and interaction network analyses demonstrated the strong correlation between m6A regulators and the genes in the signature, further supporting the results of the m6A methylation modification patterns. These findings highlight the potential utility of integrating multi-omics data (m6A methylation level and mRNA expression) to accurately obtain potential prognostic biomarkers, which may provide important insights into developing novel and effective therapies for LUAD.

2.
Exp Cell Res ; 406(1): 112735, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265287

RESUMO

Tripartite motif containing 16 (TRIM16) is a member of the tripartite motif protein family and functions as a potential tumor suppressor in several cancers. However, the specific function and clinical significance of TRIM16 in colorectal cancer (CRC) remains unclear. In this study, we observed that low TRIM16 expression was detected frequently in primary colorectal cancer (CRC) tissues and was closely associated with a better prognosis. Functional studies demonstrate that TRIM16 overexpression notably inhibits the metastasis abilities of CRC in vivo and in vitro. Mechanistically, our results demonstrated that TRIM16 directly bound and ubiquitinated Snail family transcriptional repressor 1 (Snail), an important transcriptional factor of the epithelial-mesenchymal transition (EMT) process suppressing the EMT in CRC. Additionally, our data revealed that the inhibition effect of TRIM16 on cancer metastasis was dependent on Snail degradation. Collectively, our study is the first to report that TRIM16 plays a crucial anti-tumor role in CRC tumorigenesis. We also provided novel evidence that TRIM16 might act as a prognostic and therapeutic target to assess and inhibit CRC progression.


Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Fatores de Transcrição da Família Snail/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/secundário , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Proteólise , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Análise de Sobrevida , Proteínas com Motivo Tripartido/antagonistas & inibidores , Proteínas com Motivo Tripartido/metabolismo , Carga Tumoral , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
3.
Inorg Chem ; 60(14): 10459-10467, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34180658

RESUMO

Four inorganic-organic hybrid octa-Cu cluster sandwiched polyoxotungstates (POTs), [Cu8(H2O)2(en)4(B-α-H2SiW9O34)2] (1), [Cu8(H2O)2(en)4(B-α-H2GeW9O34)2] (2), K2[Cu8(en)4(B-α-HSiW9O34)2]·6H2O (3), and K2[Cu8(en)4(B-α-HGeW9O34)2]·2H2O (4) (en = ethylenediamine), were hydrothermally made and characterized by single-crystal X-ray diffraction, infrared spectra, powder X-ray diffraction, and thermogravimetric analysis, respectively. Structure analysis reveals that the polyoxoanion of 1/2 is a discrete dimer built by two trivalent Keggin [B-α-XW9O34]10- (X = Si/Ge) fragments and one octa-Cu cluster, whereas 3 and 4 display a two-dimensional network built by octa-Cu-sandwiched POT units via substitution of coordinated water on polyanions of 1 and 2 and further expand into a three-dimensional framework via K cation bridges. Ultraviolet-visible diffuse reflectance spectra reveal that 1-4 are potential semiconductor materials. Moreover, its visible light-driven catalytic H2 evolution activity, electrochemical properties, catalysis for oxygenation reactions of thioethers, and magnetic behaviors have been investigated in detail.

4.
Chemosphere ; 274: 129685, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33540302

RESUMO

This study evaluated the spatial distributions and concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in ambient air around a municipal solid waste incineration (MSWI) plant located in eastern China in two sampling campaigns within one year. Twenty high-volume samples and 27 passive air samples were collected from May 2012 to May 2013. The mean sampling rate of the passive sampler was estimated to be 3.8 ± 1.8 m3 d-1 in summer and autumn, while the mean sampling rate was 2.8 ± 1.0 m3 d-1 in winter and spring. Hence, the annual mean sampling rate was approximately 3.2 ± 1.4 m3 d-1. The mean levels of PCDD/Fs, PCBs, PBDEs (excluding BDE-209) and BDE-209 in the passive air samples varied in the ranges of 0.086 ± 0.058-0.76 ± 0.51 pg TEQ m-3, 39 ± 26-170 ± 120 pg m-3, 3.3 ± 2.2-36 ± 24 pg m-3 and 58 ± 39-300 ± 150 pg m-3, respectively. The levels, congener profiles and spatial distributions of PCDD/Fs, PCBs and PBDEs were investigated. The results showed that the concentrations of PCDD/Fs and PCBs decreased with increasing distance from the emission source and that different sampling sites had slightly different effects. However, this trend was opposite to that observed for PBDEs. Moreover, principal component analysis (PCA) demonstrated that the MSWI emission source was the primary factor for PCDD/Fs in ambient air. Further monitoring should be conducted to evaluate the noticeable impact on the environment and human health due to exposure.


Assuntos
Poluentes Atmosféricos , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Poluentes Atmosféricos/análise , China , Dibenzofuranos , Dibenzofuranos Policlorados/análise , Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Humanos , Incineração , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análise , Resíduos Sólidos
5.
Medicine (Baltimore) ; 100(3): e24112, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546019

RESUMO

BACKGROUND: Stroke is the main cause of death and disability in the world and insomnia is a common complication of stroke patients. Insomnia will not only seriously affect the prognosis and quality of life of patients with stroke, but even cause the recurrence of stroke. Many studies have proved that acupuncture and moxibustion can effectively improve insomnia symptoms. This study will systematically evaluate the effectiveness and safety of acupuncture combined with moxibustion in treating insomnia after stroke. METHODS: The following 8 databases will be searched from the inception to October 31, 2020, including China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journal Database (VIP database), China Biomedical Literature Database (CBM), Wanfang Data Chinese Database, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Alternative Medicine Database (AMED), Excerpt Medica Database (Embase). We will also search for ongoing trials from the World Health Organization International Clinical Trial Registration Platform search portal, Chinese Clinical Trial Register, Clinical trials.gov. In addition, the reference lists of studies meeting the inclusion criteria will also be searched for achieving the comprehensive retrieval to the maximum. All randomized controlled trials of acupuncture and moxibustion in treating insomnia after stroke will be included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome is the Pittsburgh sleep quality index (PSQI), and the secondary outcomes include clinical efficacy, quality of life, and safety. RevMan V.5.4.1 will be used for meta-analysis. We will express the results as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and mean difference (MD) or standard mean difference (SMD) 95% CIs for continuous data. RESULTS: This study will provide a comprehensive review of the available evidence of acupuncture combined with moxibustion in treating insomnia after stroke. CONCLUSION: The conclusion of our study will provide the updated evidence to judge the effectiveness and safety of acupuncture combined with moxibustion for the treatment of insomnia after stroke. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020216720.


Assuntos
Moxibustão , Distúrbios do Início e da Manutenção do Sono/terapia , Acidente Vascular Cerebral/complicações , Humanos , Metanálise como Assunto , Distúrbios do Início e da Manutenção do Sono/etiologia , Revisões Sistemáticas como Assunto
6.
Sci Total Environ ; 752: 141924, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898803

RESUMO

E-waste recycling is well known for releasing halogenated organic compounds (HOCs) and heavy metals. This study investigated the occurrence and distribution of traditional and novel classes of contaminants, including chlorinated, brominated, and mixed halogenated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs, PBDD/Fs, PXDD/Fs), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and polyhalogenated carbazoles (PHCZs), in soil from an e-waste disposal site in Hangzhou. PBDEs were the most abundant, at 343-69306 ng kg-1, followed by PHCZs (896-41,362 ng kg-1), PCDD/Fs (349-19,396 ng kg-1), PCBs (51.3-1834 ng kg-1), PBDD/Fs (2.99-524 ng kg-1) and PXDD/Fs (0.104-21.2 ng kg-1). The detected target compound concentrations were generally lower than those reported in the literature for informal e-waste sites. Nevertheless, they can serve as a basis of information for evaluation and subsequent control. The toxic equivalent (TEQ) contributions from these contaminants (except PBDEs) decreased as follows: PCDD/Fs > PXDD/Fs > PHCZs > PCBs > PBDD/Fs. ΣDioxins (PCDD/Fs + PBDD/Fs + PXDD/Fs) accounted for 47.7%-97.2% of the total TEQs in the soil. OCDD, 1,2,3,4,6,7,8-HpBDF and OBDF were the dominant congeners, mainly derived from combustion and transport because of their low saturated vapor pressure. PXDFs were more abundant than PXDDs, and homologue profiles suggested a similar formation mechanism for PXDFs and PBDFs involving successive Br-to-Cl exchange. PHCZs were reported in soil from an e-waste disposal area for the first time, and their concentrations were several orders of magnitude higher than those of the other contaminants. Although the risk of human exposure in this study was estimated to be lower than the values recommended by the WHO (1-4 pg TEQ/kg bw/day), health implications still exist, and further investigations are necessary.

8.
Psychol Res Behav Manag ; 13: 939-948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204187

RESUMO

Background: The behavioral inhibition system (BIS) and behavioral activation system (BAS), which primarily underlie emotions and behaviors, are associated with depression and anxiety. However, the reasons behind these associations require further exploration. Objective: This study aims to examine the mediating effects of cognitive emotion regulation between BIS/BAS and depression/anxiety among community-dwelling elderly Chinese. Methods: A cross-sectional survey was conducted with a sample of 836 elderly individuals. Structural equation modeling was used to determine relationships among BIS/BAS, cognitive emotion regulation, and depression/anxiety. Results: Participants reporting higher BIS sensitivity were more likely to use maladaptive cognitive emotion regulation strategies, which were in turn associated with higher rates of depression and anxiety. BAS sensitivity was more likely to lead to adaptive cognitive emotion regulation strategies, which resulted in lower levels of depression and anxiety. Conclusion: Our findings suggest that incorporating emotional regulation in interventions targeting BIS/BAS sensitivities may enhance the accuracy and efficiency of these treatments for depression and anxiety.

9.
Am J Transl Res ; 12(9): 5586-5596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042440

RESUMO

Endothelial barrier dysfunction is a critical pathophysiological process of pulmonary ischemia/reperfusion (I/R) injury in patients scheduled for cardiopulmonary bypass. Impaired actin cytoskeleton dynamics and cell-cell junctions are the main causes of endothelial dysfunction. Statins have protective effects on I/R-induced lung injury; however, the mechanism is unclear. We explored the therapeutic potential of simvastatin (SV) in endothelial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). SV pretreatment promoted the barrier function of human pulmonary microvascular endothelial cells (HPMECs) subjected to OGD/R. LY294002 was used to evaluate the role of the PI3K/Akt pathway in regulating the barrier function of HPMECs subjected to OGD/R. LY294002 suppressed the barrier function of HPMECs. SV restored the endothelial barrier function by rescuing endothelial cell migration and permeability, which are involved in the regulation of cytoskeleton dynamics and intercellular junction expression via the PI3K/Akt signaling pathway.

10.
J Cancer ; 11(23): 6950-6959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123285

RESUMO

Accumulating evidence indicated that circular RNAs (circRNAs) are crucial regulators in tumorigenesis of hepatocellular carcinoma (HCC), but it is still unclear how hsa_circ_0039053 causes HCC. Herein, hsa_circ_0039053 was upregulated in HCC tissues and cell lines. The upregulation of hsa_circ_0039053 was linked to the advanced clinical characteristics of patients. Downregulation of hsa_circ_0039053 decreased the invasion and proliferative ability of tumors in vitro and as well as tumor growth in vivo. Mechanically, hsa_circ_0039053 positively regulated USP21 expression through interacting with miR-637. Moreover, overexpression of USP21 or silencing of miR-637 restored the inhibitory impacts of hsa_circ_0039053 silencing on HCC progression. Collectively, our study confirmed that hsa_circ_0039053 could be regarded as a competing endogenous RNA (ceRNA) to positively modulate the expression of USP21 combining with miR-637, which provided a potential target in HCC treatment.

11.
Gen Physiol Biophys ; 39(4): 355-362, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32902404

RESUMO

Extensive scarring normally causes hypertrophic or keloid scars. This intuitively results in psychosocial distress and reduction in life quality. Tripterine is a bioactive pentacyclic triterpenoid compound while it is still poorly understood whether it possesses an anti-scarring function. NIH/3T3 cells were administrated with tripterine at increased concentrations (0-10 µM). Antisense RNA to INK4 locus (ANRIL) was transformed into NIH/3T3 cells, and the cells transfected with empty vector (mock transfection) were used as negative control. Then, cell viability and migration were profiled by cell counting kit-8 (CCK-8) and 24-Transwell assay. Protein expression was analyzed by Western blot assay. ANRIL was quantified by quantitative reverse transcription-PCR (qRT-PCR). Tripterine administration induced the growth inhibition of NIH/3T3 cells indicated by a trend toward the decreased expression of matrix metallopeptidase (MMPs), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). This process was accompanied by the decreased phosphorylation of p65, inhibitor of nuclear factor kappa-B alpha (IκBα) and the downregulation of ß-catenin. Moreover, ANRIL expression was notably repressed by tripterine. By contrast, in ANRIL-transfected cells, the effect of tripterine was abolished. Tripterine exhibited an anti-scarring bioactivity in NIH/3T3 cells by inhibiting ANRIL, and this process was accompanied by the blockade of nuclear factor-kappa B (NF-κB) and ß-catenin cascades.


Assuntos
Cicatriz , RNA Antissenso/antagonistas & inibidores , Transdução de Sinais , Triterpenos/farmacologia , Células 3T3 , Animais , Camundongos , Fator A de Crescimento do Endotélio Vascular
12.
Int J Biochem Cell Biol ; 127: 105825, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32898690

RESUMO

OBJECTIVE: The purpose of this study was to establish and validate a nomogram to predict the prognosis in patients with non-small cell lung cancer (NSCLC) from multiple perspectives. RESULTS: A total of 98,640 eligible patients were randomly divided into a training set (n = 69,048) and a validation set (n = 29,592). The baseline characteristics of the two sets were similar. We used clinical data from patients in the training set for univariate and multivariate Cox regression analyses. Twelve independent risk factors were incorporated for constructed a prognostic nomogram. And the nomogram with a concordance index of 0.777 (95 % CI, 0.775 to 0.779) for overall survival. The calibration curve results showed that the actual survival rate was consistent with the predicted survival rate. The area under curve of the receiver operating characteristic curves demonstrated that the nomogram has a high prediction of the overall survival rate in patients with NSCLC. CONCLUSION: We have developed a nomogram with high prediction accuracy and discrimination ability, which can help clinicians making personalized survival predictions for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Nomogramas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Programa de SEER , Fatores Sexuais , Taxa de Sobrevida , Estados Unidos/epidemiologia
13.
FASEB J ; 34(9): 11900-11912, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32741018

RESUMO

Lung cancer is one of most common malignancies worldwide. We have previously identified retinoic acid-induced gene G (Rig-G) as a tumor suppressor in not only acute promyelocytic leukemia, but also in other solid tumors. However, the clinical significance of Rig-G and the underlying mechanism(s) for its biological function in lung cancer remain largely unexplored. Herein, we first compared the expression of Rig-G between lung cancer (n = 138) and normal tissues (n = 23), from public-available data sets and our patient cohort. We further analyzed the correlation of Rig-G expression with key clinico-pathological features and survival outcomes in a multi-site clinical cohort of 300 lung cancer patients. Functional studies for Rig-G were performed in cell lines, and an animal model to support clinical findings. We found that Rig-G was frequently downregulated in lung cancer tissues and cell lines, and correlated with poor prognosis in lung cancer patients. Overexpression of Rig-G led to significantly reduced cell growth and suppressed migration in A549 and NCI-H1944 cells, accompanied by reduced epithelial-mesenchymal transition. Likewise, restoration of Rig-G in Lewis lung carcinoma cells permitted development of fewer cancer metastases versus controls in an animal model. Gene expression profiling results identified p53 pathway as a key downstream target of Rig-G, and p53 inhibition by pifithrin-α caused abrogation of tumor-suppressive effects of Rig-G in lung cancer. In conclusion, we, for the first time, have identified Rig-G as a novel and important tumor suppressor, which may serve as a potential therapeutic target for restoring p53 expression in lung cancer patients.


Assuntos
Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Pulmonares/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/biossíntese , Células A549 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Proteína Supressora de Tumor p53/genética
14.
Mol Cancer ; 19(1): 117, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32713345

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear. METHODS: CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils. RESULTS: Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-ß1 (TGF-ß1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-ß1 axis. CONCLUSION: Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Exossomos/metabolismo , MicroRNAs/genética , RNA Circular/genética , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Exossomos/ultraestrutura , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Modelos Biológicos , Interferência de RNA , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Aging (Albany NY) ; 12(9): 8352-8371, 2020 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-32364530

RESUMO

Exosomes play important roles in proliferation and microenvironment modulation of many types of cancers, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells-derived exosomes in angiogenesis has not been fully discussed. In this study, the roles of microRNA-183-5p (miR-183-5p) in abundant in exosomes secreted from the CRC cells were investigated. Initially, microarray analysis was employed to determine the differentially expressed miRNAs. Exosomes isolated from CRC cells were co-cultured with HMEC-1 cells to explore the role of exosomes in angiogenesis. Further, the effects of CRC cell-derived exosomal miR-183-5p on proliferation, invasion and tube formation abilities of HMEC-1 cells were assessed. The preventative effect of exosomal miR-183-5p in vivo was measured in nude mice. Initially, it was found that FOXO1 was downregulated while miR-183-5p was upregulated in CRC. Additionally, the inhibition of miR-183-5p was suggested to suppress proliferation, invasion and tube formation abilities of HMEC-1 cells through upregulating FOXO1. Then, in vitro assays demonstrated that CRC cell-derived exosomes overexpressing miR-183-5p contributed to an enhanced proliferation, invasion and tube formation abilities of HMEC-1 cells. Furthermore, in vivo experiments confirmed the tumor-promotive effects of CRC cell-derived exosomal miR-183-5p. Collectively, our study demonstrates that the CRC cell-derived exosomes overexpressing miR-183-5p aggravates CRC through the regulation of FOXO1. Exosomes overexpressing miR-183-5p might be a potential treatment biomarker for CRC.


Assuntos
Neoplasias Colorretais/patologia , Proteína Forkhead Box O1/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neovascularização Patológica/genética , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Exossomos/metabolismo , Proteína Forkhead Box O1/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Mar Biotechnol (NY) ; 22(4): 475-487, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32418070

RESUMO

Post-transcriptional regulatory mechanisms play important roles in the regulation of long-chain (≥ C20) polyunsaturated fatty acid (LC-PUFA) biosynthesis. Here, we address a potentially important role of the miR-15/16 cluster in the regulation of LC-PUFA biosynthesis in rabbitfish Siganus canaliculatus. In rabbitfish, miR-15 and miR-16 were both highly responsive to fatty acids affecting LC-PUFA biosynthesis and displayed a similar expression pattern in a range of rabbitfish tissues. A common potential binding site for miR-15 and miR-16 was predicted in the 3'UTR of peroxisome proliferator-activated receptor gamma (pparγ), an inhibitor of LC-PUFA biosynthesis in rabbitfish, and luciferase reporter assays revealed that pparγ was a potential target of miR-15/16 cluster. In vitro individual or co-overexpression of miR-15 and miR-16 in rabbitfish hepatocyte line (SCHL) inhibited both mRNA and protein levels of Pparγ, and increased the mRNA levels of Δ6Δ5 fads2, Δ4 fads2, and elovl5, key enzymes of LC-PUFA biosynthesis. Inhibition of pparγ was more pronounced with co-overexpression of miR-15 and miR-16 than with individual overexpression in SCHL. Knockdown of miR-15/16 cluster gave opposite results, and increased mRNA levels of LC-PUFA biosynthesis enzymes were observed after knockdown of pparγ. Furthermore, miR-15/16 cluster overexpression significantly increased the contents of 22:6n-3, 20:4n-6 and total LC-PUFA in SCHL with higher 18:4n-3/18:3n-3 and 22:6n-3/22:5n-3 ratio. These suggested that miR-15 and miR-16 as a miRNA cluster together enhanced LC-PUFA biosynthesis by targeting pparγ in rabbitfish. This is the first report of the participation of miR-15/16 cluster in LC-PUFA biosynthesis in vertebrates.


Assuntos
Ácidos Graxos Insaturados/biossíntese , Peixes/genética , MicroRNAs/genética , PPAR gama/genética , Animais , Sítios de Ligação , Linhagem Celular , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Regulação da Expressão Gênica , Hepatócitos/metabolismo , MicroRNAs/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/metabolismo
17.
Med Sci Monit ; 26: e920736, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32308208

RESUMO

BACKGROUND Hypertrophic scar results from an abnormal repair response to trauma in the skin and involves fibroblasts proliferation with increased collagen deposition. Transforming growth factor-ß1 (TGF-ß1) and TGF-ß receptor type I (TGF-ßR1) are involved in tissue repair and are increased by ubiquitin-specific protease 4 (USP4). This study aimed to investigate the effects of TGF-ßR1 and USP4 in human tissue samples of hypertrophic scar and on cell proliferation and cell migration in primary fibroblast cultures in vitro. MATERIAL AND METHODS Skin excision tissue samples with adjacent normal skin were obtained from 15 patients with hypertrophic scar, which provided tissue sections and primary fibroblast culture for analysis. Immunohistochemistry detected the expression of USP4 and TGF-ßR1 in tissue sections. MicroRNA (miRNAs) expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to measure protein expression levels. Cultured skin fibroblasts were investigated using immunofluorescence staining. Fibroblast proliferation, apoptosis, and migration were measured with the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and a wound-healing assay, respectively. RESULTS The expression of USP4 and TGF-ßR1 in hypertrophic scar were increased compared with normal skin. Fibroblasts cultured from hypertrophic scar tissue showed increased expression of of USP4 and TGF-ßR1. Fibroblast transfection with USP4 short-interfering RNA (siRNA) resulted in reduced fibroblast proliferation and migration, and increased apoptosis. Downregulation of USP4 inhibited the expression of TGF-ßR1 protein and increased the expression levels of Smad7 protein. CONCLUSIONS USP4 regulated the proliferation, migration, and apoptosis of hypertrophic scar fibroblasts by regulating the TGF-ß1 signaling pathway.


Assuntos
Cicatriz Hipertrófica/metabolismo , Fibroblastos/metabolismo , Pele/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteases Específicas de Ubiquitina/biossíntese , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Cicatriz Hipertrófica/patologia , Colágeno/metabolismo , Fibroblastos/citologia , Humanos , Imuno-Histoquímica , Cultura Primária de Células , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/biossíntese , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Transdução de Sinais , Pele/citologia , Fator de Crescimento Transformador beta1/genética , Proteases Específicas de Ubiquitina/metabolismo
18.
Dalton Trans ; 49(13): 4078-4083, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32134066

RESUMO

Recently, we demonstrated that the in situ formation of a building block is an attractive synthesis strategy for creating novel clusters with controllable structures. Herein, we present the design and synthesis of the first tantaloselenite polyoxoanion [Se4(TaO2)6(OH)4O17]4- (1) and a series of lanthanide derivatives (RE3+ = Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+). In total, we report seven clusters that vary in both composition and structure but which share the same {Se4(TaO2)6} building block. The compounds are fully characterized by single-crystal X-ray diffraction, IR spectra, TG, and PXRD and their decolorization properties for RhB have also been investigated. Compound 1 exhibits good photocatalytic activity for the decolorization of RhB while the introduction of lanthanide into the framework can also maintain this activity.

19.
Yonsei Med J ; 60(12): 1187-1194, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769250

RESUMO

PURPOSE: Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (AMSCs) is critical to many disease-related disorders, such as obesity and diabetes. Studies have demonstrated that miRNA-138 (miR-138) is closely involved in adipogenesis. However, the mechanisms affected by miR-138 remain unclear. This work aimed to investigate interactions between miR-138 and lipoprotein lipase (LPL), a key lipogenic enzyme, in AMSCs. MATERIALS AND METHODS: Human AMSCs (hAMSCs) isolated from human abdomen tissue were subjected to adipogenic differentiation medium. Quantitative real-time polymerase chain reaction and Western blot assay were applied to measure the expressions of miR-138, LPL, and the two adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine enhancer binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). The relationship between miR-138 and LPL was predicted utilizing the miRTarBase database and validated by dual luciferase reporter assay. RESULTS: Showing increases in C/EBPα and PPARγ expression levels, hAMSCs were induced into adipogenic differentiation. During adipogenesis of hAMSCs, miR-138 expression was significantly downregulated. Overexpression of miR-138 by transfection inhibited hAMSCs adipogenic differentiation in vitro. Mechanically, LPL was a target of miR-138. LPL expression was upregulated during adipogenesis of hAMSCs, and this upregulation was reversed by miR-138 overexpression. Functionally, silencing of LPL by transfection exerted similar inhibition of the expressions of C/EBPα and PPARγ. Meanwhile, LPL ectopic expression was able to partly abolish the suppressive effect of miR-138 overexpression on adipogenic differentiation of hAMSCs. CONCLUSION: Upregulation of miR-138 inhibits adipogenic differentiation of hAMSCs by directly downregulating LPL.


Assuntos
Adipogenia , Tecido Adiposo/citologia , Lipase Lipoproteica/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Sequência de Bases , Células Cultivadas , Regulação para Baixo/genética , Inativação Gênica , Humanos , Lipase Lipoproteica/genética , MicroRNAs/genética , Regulação para Cima/genética
20.
J Exp Clin Cancer Res ; 38(1): 411, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533774

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP), has been demonstrated to be a vital biomarker when evaluating the prognosis of multiple cancers. Nevertheless, the potential function of HOTTIP in ovarian cancer (OC), a prevalent cancer among women worldwide, remains elusive. Hence, the current study aimed to elucidate the functional relevance of HOTTIP in the development of OC. METHODS: Positive expression of PD-L1 and IL-6 was determined using immunohistochemical staining in the collected OC and normal tissues. The correlation of IL-6 and PD-L1 was analyzed using flow cytometry, Western blot analysis as well as Pearson's correlation coefficient. The interaction among HOTTIP, c-jun and IL-6 was investigated with the use of RIP, ChIP and dual luciferase reporter gene assays. Finally, the effects of HOTTIP on T cell proliferation and infiltration were identified through gain- and loss-of-function studies in vitro and in vivo. RESULTS: HOTTIP, IL-6 and PD-L1 were all highly expressed in OC tissues. A positive correlation was observed between IL-6 and PD-L1 and that between HOTTIP and IL-6 in OC tissues. HOTTIP was noted to promote the expression of IL-6 by binding to c-jun, which resulted in a promoted PD-L1 expression in neutrophils and immune escape while inhibiting T cell proliferation as well as tumor immunotherapy. CONCLUSION: Taken together, our study unveiled that HOTTIP could promote the secretion of IL-6, and consequently up-regulate the expression of PD-L1 in neutrophils, thus inhibiting the activity of T cells and ultimately accelerating immune escape of OC cells. Our study provides a potential therapeutic strategy by targeting HOTTIP in OC.


Assuntos
Antígeno B7-H1/metabolismo , Interleucina-6/metabolismo , Neutrófilos/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/metabolismo , Evasão Tumoral , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , Linfócitos T/imunologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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