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1.
Bioengineered ; 10(1): 345-352, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411110

RESUMO

This study aimed to detect serum miR-203 expression levels in AML and explore its potential clinical significance. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure the serum miR-203 levels in 134 patients with AML and 70 healthy controls. The results demonstrated that serum miR-203 expression was significantly reduced in AML patients compared with healthy controls. Receiver operating characteristic curve (ROC) analysis revealed miR-203 could distinguish AML cases from normal controls. Low serum miR-203 levels were associated with worse clinical features, as well as poorer overall survival and relapse free survival of AML patients. Moreover, multivariate analysis confirmed low serum miR-203 expression to be an independent unfavorable prognostic predictor for AML. The bioinformatics analysis showed that the downstream genes and pathways of miR-203 was closely associated with tumorigenesis. Downregulation of miR-203 in AML cell lines upregulated the expression levels of oncogenic promoters such as CREB1, SRC and HDAC1. Thus, these findings demonstrated that serum miR-203 might be a promising biomarker for the diagnosis and prognosis of AML.


Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Antagomirs/genética , Antagomirs/metabolismo , Biomarcadores Tumorais/sangue , Carcinogênese/metabolismo , Carcinogênese/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Biologia Computacional/métodos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Perfilação da Expressão Gênica , Ontologia Genética , Histona Desacetilase 1/sangue , Histona Desacetilase 1/genética , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , Anotação de Sequência Molecular , Análise Multivariada , Proteínas de Neoplasias/sangue , Prognóstico , Curva ROC , Recidiva , Transdução de Sinais , Análise de Sobrevida , Quinases da Família src/sangue , Quinases da Família src/genética
2.
Cell Prolif ; 52(5): e12661, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31318114

RESUMO

OBJECTIVES: Circular RNAs (circRNAs) are non-coding RNAs, some of which are thought to be involved in gastric cancer development. Here, we examined the functions of circRNA hsa_circ_006100 in gastric cancer cells and an animal model of gastric cancer. MATERIALS AND METHODS: The expression of hsa_circ_006100, miR-195 and various functional genes was determined by quantitative RT-PCR. Cell viability, clone formation, apoptosis and cell migration/invasion abilities were analysed by the CCK-8 assay, crystal violet staining, Hoechst staining and Transwell assay, respectively. A tumour model was established by subcutaneously injecting tumour cells into nude mice. Levels of protein expression were analysed by Western blotting and immunohistochemistry. RESULTS: A bioinformatics analysis showed that miR-195 was negatively co-expressed with hsa_circ_006100. Patients with a high hsa_circ_006100 level or low miR-195 level had tumours with a high TNM stage, poor cellular differentiation and lymph node metastasis. miR-195 was targeted and inhibited by hsa_circ_006100. Overexpression of hsa_circ_006100 enhanced cellular viability and proliferation, while miR-195 suppressed hsa_circ_006100-enhanced cell growth and induced apoptosis in MGC-803 and AGS cells. Forced hsa_circ_006100 expression promoted the migration and invasion of MGC-803 and AGS cells, while those activities were inhibited by miR-195. Mechanistically, GPRC5A was predicted as a target of miR-195 and was upregulated in gastric cancer. A miR-195 inhibitor restored cell viability, proliferation, migration and invasion, and repressed apoptosis via GPRC5A. In vivo studies showed that knockdown of hsa_circ_006100 delayed tumour growth, reduced PCNA expression and upregulated miR-195 and BCL-2 expression which was restored by miR-195 inhibition due to GPRC5A/EGFR signalling, and changed the EMT phenotype in vivo. CONCLUSIONS: Hsa_circ_006100 functions as an oncogene in gastric cancer and exerts its effects via miR-195/GPRC5A signalling.


Assuntos
MicroRNAs/metabolismo , RNA/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Neoplasias Gástricas/patologia , Animais , Antagomirs/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA/antagonistas & inibidores , RNA/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores Acoplados a Proteínas-G/química , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais , Neoplasias Gástricas/metabolismo
3.
Cell Prolif ; 52(5): e12635, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31334580

RESUMO

OBJECTIVES: MicroRNAs are powerful regulators in hepatocellular carcinoma (HCC) tumorigenesis. MicoRNA-191 (miR-191) has been reported to play an important role in HCC, However, the regulatory mechanism is still unclear. In this study, we investigated the role of miR-191 in HCC and studied its underlying mechanisms of action. MATERIALS AND METHODS: The expression of miR-191 in HCC tissues was determined by quantitative real-time PCR (qRT-PCR). The role of miR-191 in HCC cells was examined by using both in vitro and in vivo assays. Downstream targets of miR-191 were determined by qRT-PCR and Western blot analysis. Dual-luciferase assays were performed to validate the interaction between miR-191 and its targets. RESULTS: The expression of miR-191 was significantly higher in HCC patients and a higher miR-191 expression predicted poorer prognosis. Analysis of The Cancer Genome Atlas data sets suggested that miR-191 positively correlated with cell cycle progression. Gain and loss of function assays showed that miR-191 promoted cell cycle progression and proliferation. Luciferase reporter assay showed that miR-191 directly targeted the 3'-untranslated region of KLF6 mRNA. Furthermore, circular RNA has_circ_0000204 could sponge with miR-191, resulting in inactivation of miR-191. CONCLUSIONS: Our study sheds light on the novel underlying mechanism of miR-191 in HCC, which may accelerate the development of cancer therapy.


Assuntos
Carcinoma Hepatocelular/patologia , Fator 6 Semelhante a Kruppel/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , RNA/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Bases de Dados Factuais , Progressão da Doença , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Fator 6 Semelhante a Kruppel/química , Fator 6 Semelhante a Kruppel/genética , Neoplasias Hepáticas/genética , Masculino , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , RNA/genética , Transplante Heterólogo
4.
Cell Prolif ; 52(5): e12664, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31343104

RESUMO

OBJECTIVES: Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. MATERIALS AND METHODS: We collected 15 degenerative intervertebral tissues and five healthy donors. Nucleus pulposus and annulus fibrosus cells were subcultured. miR-640 expression was determined by qPCR. Computer analysis and luciferase reporter assay were used to confirm miR-640 target genes. Immunohistochemical and immunocytochemical staining was used to trace the proinflammatory cytokines and key transductor of signalling pathways. We also used ß-galactosidase staining, flow cytometry, and cell viability assay to monitor the degenerative index. RESULTS: miR-640 overexpressed in patients derived degenerative nucleus pulposus tissues and cells. The inflammatory environment promoted miR-640 expression via NF-κB signalling pathway. In addition, miR-640 targeted to LRP1 and enhances NF-κB signal activity, which built a positive feedback loop. miR-640 inhibited the expression of ß-catenin and EP300, therefore, restrained WNT signal and induced the degeneration in nucleus pulposus cells. miR-640 inhibitor treatment exhibited the effects of anti-inflammation, reverse WNT signalling pathway exhaustion, and remission of degenerative characteristics in vitro. CONCLUSIONS: miR-640 plays an important role in the degeneration of intervertebral disc and the relative inflammatory microenvironment. It is a promising potential therapeutic target for the low back pain biotherapy.


Assuntos
Degeneração do Disco Intervertebral/patologia , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , Adolescente , Adulto , Anel Fibroso/citologia , Anel Fibroso/metabolismo , Antagomirs/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Proteína p300 Associada a E1A/metabolismo , Humanos , Interleucina-1beta/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/química , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Adulto Jovem , beta Catenina/metabolismo
5.
Cell Prolif ; 52(5): e12615, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31310044

RESUMO

OBJECTIVES: It has been widely reported that long non-coding RNAs (lncRNAs) can participate in multiple biological processes of human cancers. lncRNA HLA complex group 11 (HCG11) has been reported in human cancers as a tumour suppressor. This study focused on investigating the function and mechanism of HCG11 in glioma. MATERIALS AND METHODS: Based on The Cancer Genome Atlas (TCGA) data set and qRT-PCR analysis, the expression pattern of HCG11 was identified in glioma samples. The mechanism associated with HCG11 downregulation was determined by mechanism experiments. Gain-of-function assays were conducted for the identification of HCG11 function in glioma progression. Mechanism investigation based on the luciferase reporter assay, RIP assay and pull-down assay was used to explore the downstream molecular mechanism of HCG11. The role of molecular pathway in the progression of glioma was analysed in accordance with the rescue assays. RESULTS: HCG11 was expressed at low level in glioma samples compared with normal samples. FOXP1 could bind with HCG11 and transcriptionally inactivated HCG11. Overexpression of HCG11 efficiently suppressed cell proliferation, induced cell cycle arrest and promoted cell apoptosis. HCG11 was predominantly enriched in the cytoplasm of glioma cells and acted as a competing endogenous RNAs (ceRNAs) by sponging micro-496 to upregulate cytoplasmic polyadenylation element binding protein 3 (CPEB3). CEPB3 and miR-496 involved in HCG11-mediated glioma progression. CONCLUSIONS: HCG11 inhibited glioma progression by regulating miR-496/CPEB3 axis.


Assuntos
Glioma/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Antagomirs/metabolismo , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Progressão da Doença , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/metabolismo , Glioma/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo
6.
Cell Prolif ; 52(5): e12640, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250518

RESUMO

OBJECTIVE: We aimed to investigate the roles of the lncRNA MALAT1 in renal cell carcinoma (RCC) progression. METHODS: qRT-PCR was used for the assessment of BIRC5, miRNA-203 and MALAT1 expression. Furthermore, the targeted relationships between miR-203 and BIRC5, as well as MALAT1 and miR-203, were predicted by the miRanda/starBase database and verified by dual-luciferase reporter gene assay. The effects of MALAT1, miRNA-203 and BIRC5 on cell proliferation, cell cycle, cell apoptosis, cell invasion and cell migration were studied by using CCK-8, flow cytometry, transwell and wound healing assays, respectively. In addition, the effects of MALAT1 on RCC tumorigenesis were evaluated in vivo by nude mouse tumorigenesis. RESULTS: The expression levels of BIRC5 and MALAT1 were higher in RCC tissues and cell lines than in adjacent normal tissues and a normal renal cortex proximal tubule epithelial cell line. In contrast, the expression of miRNA-203 in RCC tissues and cell lines was higher than that in adjacent normal tissues and a normal renal cortex proximal tubule epithelial cell line. BIRC5 and MALAT1 promoted cell proliferation yet decreased the percentage of RCC cells at G0/G1 phase. CONCLUSIONS: Our study demonstrated that MALAT1 functions as a miR-203 decoy to increase BIRC5 expression in RCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Survivina/metabolismo , Idoso , Animais , Antagomirs/metabolismo , Apoptose , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Survivina/antagonistas & inibidores , Survivina/genética
7.
Chem Biol Interact ; 308: 364-371, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158334

RESUMO

BACKGROUND: Notoginsenoside R1 (NGR1) is the main saponin isolated from the roots of Panax notoginseng (Burk.) F.H. Chen (Araliaceae). This study explored the protective effects of NGR1 on human renal proximal tubular epithelial cell inflammatory damage caused by lipopolysaccharide (LPS), as well as possible internal molecular mechanisms. METHODS: Cell viability and apoptosis were assessed using CCK-8 assay and Annexin V-FITC/PI Apoptosis Detection kit, respectively. Reactive oxygen species (ROS) level was tested using DCFH-DA staining. qRT-PCR was used to measure microRNA-26a (miR-26a), interleukin 1ß (IL-1ß), IL-6 and tumor necrosis factor α (TNF-α) expressions. miRNA transfection was conducted to knock down miR-26a. The protein expression levels of key molecules related to cell apoptosis, inflammatory response and nuclear factor kappa B (NF-κB) pathway were detected using western blotting. RESULTS: LPS stimulation caused human renal proximal tubular epithelial cell viability reduction, apoptosis and inflammatory cytokines expression. NGR1 treatment protected human renal proximal tubular epithelial cells from LPS-caused viability reduction, ROS level elevation, apoptosis and inflammatory cytokines expression. Mechanistically, NGR1 enhanced miR-26a expression in LPS-treated human renal proximal tubular epithelial cells. Knockdown of miR-26a reversed the protective effect of NGR1 on LPS-treated cells. Besides, NGR1 inactivated NF-κB pathway in LPS-treated human renal proximal tubular epithelial cells via up-regulating miR-26a. CONCLUSION: NGR1 protected human renal proximal tubular epithelial cells from LPS-caused inflammatory damage at least partially via up-regulating miR-26a and then inactivating NF-κB pathway.


Assuntos
Ginsenosídeos/farmacologia , MicroRNAs/metabolismo , Regulação para Cima/efeitos dos fármacos , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Interleucina-1beta/metabolismo , Túbulos Renais Proximais/citologia , Lipopolissacarídeos/farmacologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Chem Biol Interact ; 308: 332-338, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170386

RESUMO

BACKGROUND: Sevoflurane (sevo) has been reported to be an effective neuroprotective agent in cerebral ischemia/reperfusion injury (CIRI). However, the precise molecular mechanism underlying sevo preconditioning in CIRI remains largely unknown. METHODS: A middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons after oxygen-glucose deprivation and reoxygenation (OGDR) were used as the in vivo and in vitro models of CIRI. The expression profiles of miR-181a and X chromosome-linked inhibitor-of-apoptosis protein (XIAP) in the cerebral cortex of rats and in cortical neurons were examined by qRT-PCR and Western blot, respectively. The infarct volumes were measured by TTC staining and neurological deficits in rats was determined by Zea-Longa scoring criteria. The cell viability, lactate dehydrogenase (LDH) release and apoptotic rate were detected in cortical neurons by MTT assay, LDH analysis and flow cytometry. Western blot analysis was performed to assess the expression of apoptosis-related protein. Luciferase reporter assay was used to confirm the interaction between miR-181a and XIAP. RESULTS: miR-181a was upregulated and XIAP was downregulated in rats after MCAO. Sevo preconditioning attenuated miR-181a expression and promoted XIAP level in a rat model of CIRI. Sevo preconditioning ameliorated anti-miR-181a-mediated protective effects on cerebral ischemia in rat model of CIRI, presented as the decrease of infarct volume, neurological deficit and apoptosis. Moreover, sevo pretreatment abated miR-181a-induced cellular injury in primary cortical neurons after OGD, embodied by the increase of cell viability, the reduction of LDH release and the decline of apoptosis. Furthermore, miR-181a suppressed XIAP expression by binding to its 3'UTR in cortical neurons, and sevo-mediated increase on XIAP expression was counteracted by miR-181 overexpression in OGDR-treated neurons. CONCLUSION: Sevo preconditioning protected against CIRI in vitro and in vivo possibly by inhibiting miR-181a and facilitating XIAP.


Assuntos
MicroRNAs/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Sequência de Bases , Regulação para Baixo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Proteínas Inibidoras de Apoptose/química , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Alinhamento de Sequência , Sevoflurano/farmacologia
9.
Chem Biol Interact ; 309: 108705, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31199929

RESUMO

MicroRNAs have emerged as critical mediators of cerebral ischaemia/reperfusion injury. Recent studies have demonstrated that microRNA-302b-3p (miR-302b-3p) plays an important role in regulating apoptosis and oxidative stress in various cells. However, whether miR-302b-3p is involved in regulating cerebral ischaemia/reperfusion injury-induced neuronal apoptosis and oxidative stress remains unknown. In the present study, we explored the potential function and molecular mechanism of miR-302b-3p in oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal injury, using an in vitro model of cerebral ischaemia/reperfusion injury. We found that miR-302b-3p expression was up-regulated by OGD/R treatment in neurons. The inhibition of miR-302b-3p improved cell viability, and reduced apoptosis and the production of reactive oxygen species, showing a protective effect against OGD/R-induced injury. Interestingly, miR-302b-3p was shown to target and modulate murine fibroblast growth factor 15 (FGF15). Moreover, our results showed that miR-302b-3p down-regulation contributed to the promotion of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE)-mediated antioxidant signaling associated with the inactivation of glycogen synthase kinase-3ß. However, the knockdown of FGF15 significantly reversed the miR-302b-3p inhibition-mediated protective effect in OGD/R-treated neurons. Overall, these results demonstrated that miR-302b-3p inhibition confers a neuroprotective effect in OGD/R-treated neurons by up-regulating Nrf2/ARE antioxidant signaling via targeting FGF15, providing a novel target for neuroprotection in cerebral ischaemia/reperfusion injury.


Assuntos
Hipóxia Celular , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Elementos de Resposta Antioxidante/genética , Linhagem Celular , Sobrevivência Celular , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Fatores de Crescimento de Fibroblastos/genética , Glucose/deficiência , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neurônios/citologia , Neurônios/metabolismo , Neuroproteção , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Regulação para Cima
10.
Chem Biol Interact ; 309: 108716, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31207222

RESUMO

BACKGROUND: Neferine (NEF) is a major bisbenzylisoquinline alkaloid mainly exists in the seed embryo of Nelumbo nucifera (Gaertn.) that possesses anti-tumor effects. Our study designed to check the effect of NEF on breast cancer MDA-MB-231 cells and further explore the potential mechanism. METHODS: MDA-MB-231 cells were administrated with various dosages of NEF for 24 h after which cell viability was measured. The effects of NEF on cell proliferation, apoptosis, migration and invasion were assessed by BrdU staining, flow cytometry assay and Transwell assay. Western blot was utilized to assess the accumulation of proteins related with proliferation, apoptosis, metastasis, PI3K/AKT and MEK/ERK pathways. RESULTS: Viability was efficiently reduced by NEF in a dose-dependent manner. NEF (8 µM) significantly suppressed cell proliferation, migration and invasion but enhanced apoptosis in MDA-MB-213 cells. Interestingly, NEF suppressed miR-374a expression and miR-374a mediated the inhibitory effect of NEF. Moreover, miR-374a positively regulated FGFR-2 expression and FGFR-2 overexpression impeded the effect of NEF on MDA-MB-213 cells. FGFR-2 overexpression abolished the suppressive effect of NEF on PI3K/AKT and MEK/ERK pathways. CONCLUSION: We found that NEF possessed the anti-growth and anti-metastasis effect on MDA-MB-231 cells through regulating miR-374a/FGFR-2, which might provide new insight for breast cancer management.


Assuntos
Benzilisoquinolinas/farmacologia , Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Antagomirs/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Transdução de Sinais/efeitos dos fármacos
11.
Chem Commun (Camb) ; 55(52): 7466-7469, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31184647
12.
Mol Med Rep ; 19(6): 4935-4945, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059086

RESUMO

Previous reports have indicated a potential link between microRNA (miR)­214 and hypoxia. In the present study, the biological functions and potential mechanisms of miR­214 were determined, as well as its correlation with HIF­1α signaling in non­small cell lung cancer (NSCLC) cells. Quantitative polymerase chain reaction revealed that miR­214 expression was upregulated in lung cancer tissues compared with adjacent normal tissues. miR­214 mimics were transfected into A549 cells, and MTT, colony formation, invasion and wound healing assays were performed. It was demonstrated that miR­214 mimic transfection promoted the invasion, proliferation and migration of A549 cells. Furthermore, miR­214 inhibitor transfection decreased H1299 cell invasion, proliferation and migration. Next, the association between miR­214 expression and the HIF­1α signaling cascade was examined. It was demonstrated that miR­214 mimics upregulated the expression of hypoxia­inducible factor (HIF)­1α, vascular endothelial growth factor (VEGF), adenylate kinase 3 and matrix metalloproteinase (MMP)2, whereas miR­214 inhibitor downregulated the expression of these factors. Using prediction software, it was demonstrated that tumor suppressor ING4 was a target of miR­214. A luciferase reporter assay confirmed that ING4 was a direct target of miR­214. There was a negative correlation between ING4 and miR­214 expression in lung cancer tissues. In addition, ING4 siRNA and plasmid was transfected into cells in order to validate its effect on HIF­1α, MMP2 and VEGF expression. ING4 overexpression downregulated HIF­1α and its targets MMP2 and VEGF, while ING4 siRNA upregulated HIF­1α, MMP2 and VEGF. In conclusion, it was demonstrated that miR­214 targeted ING4 in lung cancer cells, and upregulated the HIF­1α cascade, leading to MMP2 and VEGF upregulation. This approach may help to clarify the role of miRNA in non­small lung cancer and may be a new therapeutic target for non­small lung cancer.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Homeodomínio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células A549 , Adenilato Quinase/genética , Adenilato Quinase/metabolismo , Adulto , Idoso , Antagomirs/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Fator A de Crescimento do Endotélio Vascular/genética
13.
Mol Med Rep ; 19(6): 5335-5344, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059047

RESUMO

MicroRNAs (miRs) have been identified as critical regulatory molecules in myocardial ischemia/reperfusion injury; however, the exact expression profile of miR­199a­5p in reperfusion injury and the underlying pathogenic mechanisms remain unclear. In the present study, it was revealed that miR­199a­5p expression was significantly increased in the plasma of patients with acute myocardial infarction and in a H9c2 cell model of oxygen­glucose deprivation and reperfusion (OGD/R) via reverse transcription­quantitative PCR. H9c2 cells were transfected with miR­199a­5p mimic or inhibitor, or short interfering RNA (siRNA) specific to hypoxia­inducible factor­1α (HIF­1α). MTS, lactate dehydrogenase (LDH), TUNEL staining and flow cytometry assays were performed to determine the proliferation, LDH activity, apoptosis and mitochondrial membrane potential (ΔΨm) of H9c2 cells, respectively. The overexpression of miR­199a­5p in the OGD/R cell model significantly decreased the viability and increased the lactate dehydrogenase leakage of cells; whereas knockdown of miR­199­5p induced the opposing effects. Additionally, inhibition of miR­199­5p significantly attenuated OGD/R­induced alterations to the mitochondrial transmembrane potential (ΔΨm) and increases in the apoptosis of cells. Furthermore, the overexpression or knockdown of miR­199a­5p decreased or increased the expression of HIF­1α and phosphorylation of glycogen synthase kinase 3ß (GSK3ß) in OGD/R­treated H9c2 cells. Additionally, siRNA­mediated downregulation of HIF­1α decreased phosphorylated (p)­GSK3ß (Ser9) levels and reversed the protective effects of miR­199a­5p inhibition on OGD/R­injured H9c2 cells. Similarly, treatment with LiCl (a specific inhibitor of p­GSK3ß) also attenuated the protective effects of miR­199a­5p knockdown on OGD/R­injured H9c2 cells. Mechanistic studies revealed that HIF­1α was a target of miR­199a­5p, and that HIF­1α downregulation suppressed the expression of p­GSK3ß in OGD/R­injured H9c2 cells. Furthermore, an miR­199a­5p inhibitor increased the interaction between p­GSK3ß and adenine nucleotide transferase (ANT), which was decreased by OGD/R. Additionally, miR­199a­5p inhibitor reduced the OGD/R­induced interaction between ANT and cyclophilin D (Cyp­D), potentially leading to the increased mitochondrial membrane potential in inhibitor­transfected OGD/R­injured H9c2 cells. Collectively, the present study identified a novel regulatory pathway in which the upregulation of miR­199a­5p reduced the expression of HIF­1α and p­GSK3ß, and potentially suppresses the interaction between p­GSK3ß and ANT, thus promoting the interaction between ANT and Cyp­D and potentially inducing cytotoxicity in OGD/R­injured H9c2 cells.


Assuntos
Hipóxia Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/patologia , Adulto , Animais , Antagomirs/metabolismo , Sobrevivência Celular , Regulação para Baixo , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Potencial da Membrana Mitocondrial , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Oxigênio/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Transdução de Sinais
14.
Mol Med Rep ; 19(6): 5345-5352, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059054

RESUMO

Myofibroblast transdifferentiation is an important feature of cardiac fibrosis. Previous studies have indicated that microRNA­216a (miR­216a) is upregulated in response to transforming growth factor­ß (TGF­ß) in kidney cells and can activate Smad3; however, its role in myofibroblast transdifferentiation remains unclear. The present study aimed to investigate the role of miR­216a in TGF­ß­induced myofibroblast transdifferentiation, and to determine the underlying mechanisms. Adult mouse cardiac fibroblasts were treated with TGF­ß to induce myofibroblast transdifferentiation. An antagomir and agomir of miR­216a were used to inhibit or overexpress miR­216a in cardiac fibroblasts, respectively. Myofibroblast transdifferentiation was evaluated based on the levels of fibrotic markers and α­smooth muscle actin expression. The miR­216a antagomir attenuated, whereas the miR­216a agomir promoted TGF­ß­induced myofibroblast transdifferentiation. Mechanistically, miR­216a accelerated myofibroblast transdifferentiation via the AKT/glycogen synthase kinase 3ß signaling pathway, independent of the canonical Smad3 pathway. In addition, it was observed that miR­216a activated AKT via the downregulation of PTEN. In conclusion, miR­216a was involved in the regulation of TGF­ß­induced myofibroblast transdifferentiation, suggesting that targeting miR­216a may aid in developing effective interventions for the treatment of cardiac fibrosis.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Regulação para Baixo , Glicogênio Sintase Quinase 3 beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Miofibroblastos/citologia , Miofibroblastos/metabolismo , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína Smad3/metabolismo
15.
Mol Med Rep ; 19(6): 5397-5405, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059060

RESUMO

NORAD (non­coding RNA activated by DNA damage) is a long non­coding RNA (lncRNA) that is upregulated and promotes cell progression in various human types of cancer; however, its function in non­small cell lung cancer (NSCLC) remains unclear. The present study investigated the regulatory function and underlying mechanisms of NORAD in NSCLC. NORAD and miR­136­5p expression were assessed by reverse transcription­quantitative polymerase chain reaction, and proliferation and glycolysis­associated markers were also assessed. Direct miR­136­5p regulation by NORAD was detected using luciferase reporter assay and RNA immunoprecipitation. NORAD was highly expressed in NSCLC tissues and cell lines. NORAD overexpression increased NSCLC proliferation and glycolysis. Further investigation revealed that NORAD serves as a competing endogenous RNA for miR­136­5p. Gain­ and loss­of­function experiments confirmed that miR­136­5p reversed the promoting effects of NORAD in NSCLC. Results of the present study indicate that NORAD serves as a growth­promoting lncRNA in NSCLC by suppressing the function of miR­136­5p. NORAD and miR­136­5p interaction may provide a potential target for NSCLC treatment.


Assuntos
Proliferação de Células , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Antagomirs/metabolismo , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Glicólise , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência
16.
Mol Med Rep ; 19(6): 5361-5367, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059093

RESUMO

A substantial body of research has confirmed that Vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a role in contributing to the high interpatient variability in the warfarin maintenance dose. The aim of the present study was to examine the impact of SNPs of miR­137 on the warfarin maintenance dose. Computational analysis and luciferase assay were used to search the targets of miR­137, and luciferase assay was also used to confirm the effect of the polymorphisms on the transcription of the promoter. The regulatory relationship between miR­137 and VKORC1 was detected using real­time PCR. We then performed statistical analysis to find the warfarin maintenance dose in the different groups. A total of 155 subjects were enrolled in our research, and the characteristics of the patients were collected. Using computational analysis, we identified that miR­137 binds to the VKORC1 3'untranslated region (3'UTR) and regulates the expression of VKORC1. This hypothesis was confirmed by luciferase reporter assay as miR­137 significantly reduced the VKORC1 3'UTR luciferase activity, while the luciferase activity of mutant VKORC1 3'UTR was similar to the scramble control. According to the result of the luciferase reporter assay, we found that miR­137 SNP with the presence of the A allele apparently reduced the luciferase activity. Using real­time PCR, we revealed that miR­137 negatively regulated the expression of VKORC1 in a concentration­dependent manner in liver cells. Furthermore, no difference was noted regarding the warfarin maintenance dose between the different age or gender groups, and furthermore AC + AA carriers showed a markedly higher warfarin maintenance dose than CC carriers. These findings collectively provide support that VKORC1 is a direct target of miR­137 and the miR­137 rs2660304 polymorphism is associated with warfarin maintenance dose in patients with atrial fibrillation. The rs2660304 polymorphism is a potential biomarker for predicting the clinical efficacy of warfarin in these patients.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Variação Genética , MicroRNAs/genética , Varfarina/uso terapêutico , Regiões 3' não Traduzidas , Adulto , Alelos , Antagomirs/metabolismo , Fibrilação Atrial/genética , Fibrilação Atrial/patologia , Relação Dose-Resposta a Droga , Feminino , Genótipo , Células Hep G2 , Humanos , Coeficiente Internacional Normatizado , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Vitamina K Epóxido Redutases/química , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo
17.
Mol Med Rep ; 19(6): 5301-5308, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059108

RESUMO

Temozolomide (TMZ) is widely used as a chemotherapeutic agent in the treatment of glioma; however, the development of drug resistance remains a major obstacle in the effective treatment of glioblastoma. Increasing evidence has indicated that microRNAs (miRs) are involved in the drug resistance of glioma; however, the role of miR­186­5p in the TMZ resistance of glioblastoma remains unknown. In the present study, the role of miR­186­5p in the resistance of glioblastoma to TMZ was investigated. mRNA and protein expression levels were detected via reverse transcription­quantitative PCR and western blot analysis, respectively. It was determined that miR­186­5p was significantly downregulated in glioblastoma tissues and cell lines. Additionally, the expression of miR­186­5p was decreased, whereas that of Twist1 was upregulated during the development of drug resistance in glioma cells. The introduction of miR­186 into glioblastoma cells via transfection decreased the proliferation and TMZ resistance of glioblastoma cells, as determined via 5­ethynyl­2'­deoxyuridine and Cell Counting Kit­8 assays, whereas the inhibition of miR­186­5p induced opposing effects. Furthermore, luciferase reporter and expression rescue assays revealed that miR­186­5p bound to the 3'­untranslated region of Twist­related protein 1 (Twist1). In conclusion, the present study demonstrated that downregulation of miR­186­5p may contribute to the proliferation and drug resistance of glioblastoma cells via the regulation of Twist1 expression. These results suggested that miR­186­5p may be a novel therapeutic target in the treatment of glioblastoma.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Regiões 3' não Traduzidas , Adulto , Idoso , Antagomirs/metabolismo , Neoplasias Encefálicas/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Glioblastoma/metabolismo , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Temozolomida/farmacologia , Proteína 1 Relacionada a Twist/antagonistas & inibidores , Proteína 1 Relacionada a Twist/genética
18.
Chem Biol Interact ; 308: 244-251, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31145890

RESUMO

Increasing evidence has shown that dysregulation of microRNA-621 (miR-621) is demonstrated to be associated with several cancers. However, the role of miR-621 in bladder cancer (BCa) remains unclear. Herein, we aimed to study the expression pattern, biological function, and molecular mechanism of miR-621 in BCa. First, we demonstrated that miR-621 was frequently downregulated in BCa tissues and cell lines compared with the adjacent normal BCa tissues and non-cancerous immortalized urothelial cell line. In addition, the expression of miR-621 was negatively correlated with overall survival of BCa patients. Functional experiments suggessted that miR-621 inhibited the proliferation and metastasis of BCa cells. Notably, dual-luciferase assay showed that miR-621 directly targeted the 3' UTR of TRIM29, which was frequently upregulated in BCa tissues and displayed inverse correlation with miR-621 expression. Furthermore, we demonstrated that miR-621 inhibited the proliferation and metastasis of BCa cells via Wnt/ß-catenin signaling pathway by targeting TRIM29. Our study suggested that the miR-621/TRIM29 axis inhibits the proliferation and metastasis of BCa cells via Wnt/ß-catenin signaling pathway and may have potential applications for development of BCa diagnosis or treatment.


Assuntos
Proliferação de Células , MicroRNAs/metabolismo , Via de Sinalização Wnt , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Alinhamento de Sequência , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
19.
Mol Med Rep ; 19(6): 5203-5210, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059039

RESUMO

The aim of the current study was to investigate the expression and role of microRNA­486­5p (miR­486­5p) in hypertrophic scar (HS) formation, and to examine the associated mechanisms. First, miR­486­5p expression was detected in HS tissues and human hypertrophic scar fibroblasts (hHSFs) by reverse transcription­quantitative polymerase chain reaction. Target genes of miR­486­5p were predicted using TargetScan and verified by dual­luciferase reporter assays. To investigate the role of miR­486­5p in HS formation, miR­486­5p was overexpressed in hHSFs through transfection with miR­486­5p mimics. MTT, cell apoptosis and cell cycle assays were preformed to investigate the proliferation, cell apoptosis and cell cycle distribution of hHSFs, respectively. Additionally, protein expression was measured by western blot analysis. The results demonstrated that miR­486­5p expression was significantly decreased in HS tissues and cells. Mothers against decapentaplegic homolog (Smad)2 was a target gene of miR­486­5p, and it was negatively regulated by miR­486­5p. It was also found that Smad2 expression was significantly increased in HS tissues and cells. Further analysis indicated that miR­486­5p mimic transfection inhibited the proliferation, induced cell apoptosis and increased G1/S phase arrest in hHSFs. Furthermore, the expression of cyclin­dependent kinase (CDK)2, CDK4 and apoptosis regulator Bcl­2 was repressed, while apoptosis regulator BAX expression was enhanced by miR­486­5p mimic transfection. Notably, the effects of miR­486­5p mimic on hHSFs were significantly eliminated by Smad2 plasmid transfection. Taken together, these results demonstrated that miR­486­5p inhibited the proliferation, induced apoptosis and increased G1/S phase arrest of hHSFs by targeting Smad2. miR­486­5p may be a promising therapeutic target for HS management.


Assuntos
Cicatriz Hipertrófica/patologia , MicroRNAs/metabolismo , Proteína Smad2/metabolismo , Regiões 3' não Traduzidas , Adulto , Antagomirs/metabolismo , Apoptose , Proliferação de Células , Cicatriz Hipertrófica/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Smad2/química , Proteína Smad2/genética , Proteína X Associada a bcl-2/metabolismo
20.
Mol Med Rep ; 19(6): 5227-5236, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059052

RESUMO

Psoriasis is a chronic inflammatory disease characterized by the abnormal differentiation and hyperproliferation of epidermal keratinocytes. The aim of the present study was to investigate the mechanism by which microRNA­125b (miR­125b) inhibits the activation of the bromodomain­containing protein 4 (BRD4)/Notch signaling pathway in psoriasis. The contents of associated miRNAs in serum samples from 32 patients with psoriasis were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The most significantly downregulated miRNA, miR­125b, was screened out. In experiments using HaCaT cells, the association between miR­125b and cell proliferation was observed using a Cell Counting Kit­8 assay, that between miR­125b and the Notch signaling pathway was observed by western blotting and RT­qPCR, and that between miR­125b and the upstream molecule BRD4 of the Notch signaling pathway was observed by luciferase reporter assay and western blotting. The proliferation of HaCaT cells became apparent following miR­125b inhibition. The Jagged­1 ligand in the Notch signaling pathway was upregulated, the active intracellular domain of the Notch1 receptor was increasingly truncated, and the Notch signaling pathway was activated. Furthermore, the inhibited miR­125b contributed directly toward the upstream protein BRD4 3'­UTR of Jagged­1, ultimately activating the Notch signaling pathway with the upregulation of Jagged­1. In conclusion, the proliferation of HaCaT cells mediated by the Jagged­1/Notch signaling pathway was decreased with the miR­125b­mediated inhibition of BRD4 expression. Therefore, miR­125b may be a biomarker and potential therapeutic target for psoriasis treatment.


Assuntos
Proliferação de Células , Proteína Jagged-1/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Psoríase/patologia , Receptores Notch/metabolismo , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Adolescente , Adulto , Antagomirs/metabolismo , Linhagem Celular , Sobrevivência Celular , Feminino , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , MicroRNAs/genética , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Psoríase/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Adulto Jovem
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