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1.
Artigo em Inglês | MEDLINE | ID: mdl-32191117

RESUMO

Premature infants are often exposed to positive pressure ventilation and supplemental oxygen, which leads to the development of chronic lung disease (CLD). There are currently no standard serum biomarkers used for prediction or early detection of patients who go on to develop CLD. MicroRNAs (miRNAs) are a novel class of naturally occurring, short, noncoding substances that regulate gene expression at the posttranscriptional level and cause translational inhibition and/or mRNA degradation and present in body fluids packaged in extracellular vesicles (EVs), rendering them remarkably stable. Our aim was to evaluate miRNAs identified in serum EVs of premature infants as potential biomarkers for CLD. Serum EVs were extracted from premature infants at birth and on the 28th day of life (DOL). Using a human miRNA array, we identified 62 miRNAs that were universally expressed in CLD patients and non-CLD patients. Of the 62 miRNAs, 59 miRNAs and 44 miRNAs were differentially expressed on DOL0 and DOL28 in CLD and non-CLD patients, respectively. Of these miRNAs, serum EV miR-21 was upregulated in CLD patients on DOL28 compared with levels at birth and downregulated in non-CLD patients on DOL28 compared with levels at birth. In neonatal mice exposed to hyperoxia for 7days, as a model of CLD, five miRNAs (miR-34a, miR-21, miR-712, miR-682, and miR-221) were upregulated, and 7 miRNAs (miR-542-5p, miR-449a, miR-322, miR-190b, miR-153, miR-335-3p, miR-377) were downregulated. MiR-21 was detected as a common miRNA that changed in CLD patients and in the hyperoxia exposed mice. We conclude that EV miR-21 may be a biomarker of CLD.


Assuntos
Hiperóxia/diagnóstico , Hiperóxia/genética , Pneumopatias/diagnóstico , Pneumopatias/genética , MicroRNAs/genética , Animais , Animais Recém-Nascidos , Antagomirs/genética , Antagomirs/metabolismo , Biomarcadores/metabolismo , Doença Crônica , Modelos Animais de Doenças , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Hiperóxia/sangue , Hiperóxia/fisiopatologia , Recém-Nascido , Recém-Nascido Prematuro , Pneumopatias/sangue , Pneumopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , MicroRNAs/classificação , Análise de Sequência com Séries de Oligonucleotídeos , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Prognóstico
2.
Chem Biol Interact ; 322: 109027, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147387

RESUMO

OBJECTIVE: Evidence has shown that sevoflurane plays a protective role in acute lung injury (ALI) due to its anti-inflammatory and apoptotic-regulating activity. Nevertheless, the mechanism of sevoflurane is still not completely understood. This study intends to discuss the mechanism of sevoflurane on ALI and the possible mechanisms involved. METHODS: ALI model of rats was established through intravenous injection of endotoxin lipopolysaccharide. microRNA-34a-3p (miR-34a-3p) and signal transducers and activators of transcription 1 (STAT1) expression in lung tissues of ALI rats were detected. The optimal inhaled concentration of sevoflurane was screened, and then the modeled rats were injected with miR-34a-3p inhibitors, overexpressed STAT1 and inhaled 1.0 Minimum Alveolar Concentration (MAC) sevoflurane to determine mean arterial pressure (MAP) of rats, wet weight/dry weight ratio and myeloperoxidase (MPO) activity, oxidative stress- and inflammation-related factors in lung tissues of rats, along with lung cell viability and apoptosis. RESULTS: MiR-34a-3p was downregulated while STAT1 was upregulated in ALI rats. Sevoflurane of 1.0 MAC was selected as the optimal inhalation concentration. Sevoflurane (1.0 MAC) increased MAP at T3 and reduced MPO activity, alleviated pathological damage, suppressed apoptosis, oxidative stress and inflammation, and induced cell viability in lung tissues of ALI rats. Down-regulated miR-34a-3p or up-regulated STAT reversed the functions of sevoflurane (1.0 MAC) on ALI rats. CONCLUSION: Collectively, we demonstrate that sevoflurane reduces inflammatory factor expression, increases lung cell viability and inhibits lung cell apoptosis in ALI through upregulation of miR-34a-3p and downregulation of STAT1, which provides new clues for ALI treatment.


Assuntos
Apoptose , Pulmão/metabolismo , MicroRNAs/metabolismo , Fator de Transcrição STAT1/metabolismo , Sevoflurano/administração & dosagem , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/veterinária , Administração por Inalação , Animais , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT1/antagonistas & inibidores , Fator de Transcrição STAT1/genética , Sevoflurano/farmacologia , Regulação para Cima/efeitos dos fármacos
3.
Biochem Biophys Res Commun ; 524(4): 791-797, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32019676

RESUMO

Increased granulosa cell (GC) proliferation may contribute to abnormal folliculogenesis in patients with polycystic ovary syndrome (PCOS), which affects approximately 10% reproductive aged women. However, the mechanisms underlying increased GC proliferation in PCOS remain incompletely understood. In this study, we identified miR-3940-5p as a hub miRNA in GC from PCOS using weighted gene co-expression network analysis (WGCNA), and real-time polymerase chain reaction (RT-PCR) analysis confirmed that miR-3940-5p was significantly increased in GC from PCOS. Enrichment analysis of predicted target genes of miR-3940-5p indicated potential roles of miR-3940-5p in follicular development and cell proliferation regulation. Consistently, functional study confirmed that miR-3940-5p overexpression promoted granulosa cell proliferation. Integrated analysis of mRNA expression profiling data and predicted target genes of miR-3940-5p identified potassium voltage-gated channel subfamily A member 5 (KCNA5) as a potential target of miR-3940-5p, and was validated by luciferase reporter assay. Finally, functional analysis suggested that miR-3940-5p promoted GC proliferation in a KCNA5 dependent manner. In conclusion, miR-3940-5p was a hub miRNA upregulated in GC from PCOS, and promoted GC proliferation by targeting KCNA5.


Assuntos
Regulação Neoplásica da Expressão Gênica , Células da Granulosa/metabolismo , Canal de Potássio Kv1.5/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Síndrome do Ovário Policístico/genética , Adulto , Antagomirs/genética , Antagomirs/metabolismo , Proliferação de Células , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Genes Reporter , Células da Granulosa/patologia , Humanos , Canal de Potássio Kv1.5/antagonistas & inibidores , Canal de Potássio Kv1.5/metabolismo , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Proteínas de Neoplasias/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
4.
Cell Biochem Biophys ; 78(1): 89-100, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32026263

RESUMO

Immunological aging impairs immune system protection in the body and is associated with high morbidity and mortality in aged people. Electroacupuncture (EA) has been proven to boost immunity. The purpose of this study was to identify the effect of EA on miRNA expression in the immune system of senescence-accelerated mouse P8 (SAMP8) mice. We utilized SAMP8 mice as an aging model and detected the altered expression of miRNAs in CD4+ T cells after EA stimulation by deep sequencing. Differentially expressed miRNAs in different groups were identified using Venn diagrams and functional analysis was performed. The effect of EA on the expression of the identified miRNAs was investigated in natural-aged C57BL/6J mice and the biological functions of miR-301a-3p and miR-181a-1-3p in CD4+ T cells were identified. Four upregulated and two downregulated miRNAs were identified in group I (EA-SAMP8 vs. shEA-SAMP8); 41 upregulated and nine downregulated miRNAs were identified in group II (EA-SAMP8 vs. SAMP8); 42 upregulated and eight downregulated miRNAs were identified in group III (shEA-SAMP8 vs. SAMP8). The three groups shared four overlapping differentially expressed miRNAs, and 10 miRNAs were only found in group II. Gene Ontology enrichment analysis of these 14 miRNAs revealed that their target genes were enriched in 229 "biological process" categories. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the targets were significantly mapped in 76 pathways. Furthermore, five significant pathways were involved in T cell differentiation. MiRNA-gene-net showed that miR-582-5p, miR-17-5p, miR-144-3p, miR-451a, and miR-301a-3p regulated the most important target genes in these pathways. The expression of these miRNAs was also regulated by EA in aged C57BL/6J mice. In addition, miR-301a-3p was involved in regulating the expression of inflammatory factors by mediating the differentiation of CD4+ T cells in C57BL/6J mice. Analysis of miRNAs indicated that EA contributes to maintaining the balance of CD4+ T cell differentiation in the aging immune system. These results provide novel insights into the effect of EA in immunological aging.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Eletroacupuntura , MicroRNAs/metabolismo , Baço/metabolismo , Envelhecimento , Animais , Antagomirs/metabolismo , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular , Citocinas/análise , Citocinas/metabolismo , Regulação para Baixo , Feminino , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Análise de Sequência de RNA , Regulação para Cima
5.
PLoS One ; 15(1): e0227568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929567

RESUMO

BACKGROUND: Increasing evidence has suggested that multiple long non-coding RNAs (lncRNAs) act key regulatory functions in the pathogenesis of bladder cancer. This study aimed to determine the expression and clinical significance of lncRNA ROR1 antisense RNA 1 (ROR1-AS1) from patients with bladder cancer, and to explore the potential role and mechanism underlying ROR1-AS1-related cancer progression. METHODS: Real time quantitative PCR (RT-qPCR) was conducted to detected the expression levels of ROR1-AS1 and miR-504 in bladder cancer samples and cell lines. Chi-square test was used for correlation analysis. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and wound scratch assays were applied to assesses the effects of ROR1-AS1 overexpression and knockdown on bladder cancer cell growth and migration in vitro, respectively. The prognosis of bladder cancer patients was evaluated by survival curves with Kaplan-Meier method. The regulatory mechanism of ROR1-AS1 on miR-504 was confirmed by bioinformatics analysis and luciferase reporter gene assay. RESULTS: ROR1-AS1 levels were obviously upregulated in bladder cancer tissues than matched normal bladder tissues. High expression of ROR1-AS1 was remarkably correlated with higher histological grade, advanced tumor stage, and positive lymph node metastasis. High ROR1-AS1 expression was markedly correlated with shorter overall survival of bladder cancer patients. Moreover, knockdown of ROR1-AS1 notably repressed T24 and 5637 cell growth and migration. ROR1-AS1 directly bound with miR-504 and act as a molecular sponge to decrease miR-504 expression. Silencing of miR-504 partly abrogated ROR1-AS1 knockdown-induced inhibitory effects on bladder cancer cell growth and migration. CONCLUSIONS: Our data demonstrated that increased ROR1-AS1 promotes cell growth and migration of bladder cancer via regulation of miR-504, indicating ROR1-AS1 may be used as a prognostic biomarker and therapeutic target for bladder cancer.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/patologia , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade
6.
Cell Biochem Biophys ; 78(1): 77-88, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31811601

RESUMO

Circular RNAs (cicRNAs) have been identified to play pivotal roles in several cancer types. However, functions of circRNA in malignant melanoma are poor defined. Our current study demonstrated that human circMYC was obviously upregulated in human melanoma tissue. Furthermore, circMYC promoted the proliferation of human melanoma cells and Mel-CV cells. The expression of circMYC can repress Mel-CV cell glycolysis and LDHA activities in the in vitro glycolysis and lactate production evaluations. circMYC directly bound to miR-1236 as a molecular sponge that targeting miR-1236 in Mel-CV cells via bioinformatics analysis, pull-down assay, and luciferase reporter assays. Our present study revealed that 3' UTR of LDHA acted as a target of miR-1236 using Mel-CV cells. Based on our findings, c-MYC-SRSF1 axis may regulate the production of circMYC. Overall, these results elucidate potential effects of circMYC in melanoma development and provide a promising biomarker for melanoma diagnosis.


Assuntos
Proliferação de Células , Glicólise , RNA Circular/metabolismo , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Humanos , L-Lactato Desidrogenase/química , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Ácido Láctico/metabolismo , Melanoma/metabolismo , Melanoma/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Circular/antagonistas & inibidores , RNA Circular/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo
7.
Cell Mol Life Sci ; 77(18): 3643-3655, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31873757

RESUMO

Prior studies have established the important role of extracellular signal-regulated kinase 1/2 (ERK1/2) as a mediator of acute kidney injury (AKI). We demonstrated rapid ERK1/2 activation induced renal dysfunction following ischemia/reperfusion (IR)-induced AKI and downregulated the mitochondrial biogenesis (MB) regulator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in mice. In this study, ERK1/2 regulation of cellular nicotinamide adenine dinucleotide (NAD) and PGC-1α were explored. Inhibition of ERK1/2 activation during AKI in mice using the MEK1/2 inhibitor, trametinib, attenuated renal cortical oxidized NAD (NAD+) depletion. The rate-limiting NAD biosynthesis salvage enzyme, NAMPT, decreased following AKI, and this decrease was prevented by ERK1/2 inhibition. The microRNA miR34a decreased with the inhibition of ERK1/2, leading to increased NAMPT protein. Mice treated with a miR34a mimic prevented increases in NAMPT protein in the renal cortex in the presence of ERK1/2 inhibition. In addition, ERK1/2 activation increased acetylated PGC-1α, the less active form, whereas inhibition of ERK1/2 activation prevented an increase in acetylated PGC-1α after AKI through SIRT1 and NAD+ attenuation. These results implicate IR-induced ERK1/2 activation as an important contributor to the downregulation of both PGC-1α and NAD+ pathways that ultimately decrease cellular metabolism and renal function. Inhibition of ERK1/2 activation prior to the initiation of IR injury attenuated decreases in PGC-1α and NAD+ and prevented kidney dysfunction.


Assuntos
Lesão Renal Aguda/patologia , Citocinas/metabolismo , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Acetilação/efeitos dos fármacos , Lesão Renal Aguda/metabolismo , Animais , Antagomirs/metabolismo , Creatinina/sangue , Citocinas/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Córtex Renal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação/efeitos dos fármacos , Piridonas/farmacologia , Pirimidinonas/farmacologia , Sirtuína 1/metabolismo
8.
PLoS One ; 14(12): e0226192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31825987

RESUMO

Visceral Leishmaniasis is a chronic zoonosis and, if left untreated, can be fatal. Infected dogs have decreased cellular immunity (Th1) and develop a potent humoral response (Th2), which is not effective for elimination of the protozoan. Immune response can be modulated by microRNAs (miRNAs), however, characterization of miRNAs and their possible regulatory role in the spleen of infected dogs have not been done. We evaluated miRNA expression in splenic leukocytes (SL) from dogs naturally infected with Leishmania infantum and developing leishmaniasis (CanL; n = 8) compared to healthy dogs (n = 4). Microarray analysis showed increased expression of miR 21, miR 148a, miR 7 and miR 615, and downregulation of miR 150, miR 125a and miR 125b. Real-time PCR validated the differential expression of miR 21, miR 148a and miR 615. Further, decrease of miR 21 in SL, by means of transfection with a miR 21 inhibitor, increased the IL-12 cytokine and the T-bet/GATA-3 ratio, and decreased parasite load on SL of dogs with CanL. Taken together, these findings suggest that L. infantum infection alters splenic expression of miRNAs and that miR 21 interferes in the cellular immune response of L. infantum-infected dogs, placing this miRNA as a possible therapeutic target in CanL.


Assuntos
Doenças do Cão/diagnóstico , Interleucina-12/metabolismo , Leishmaniose Visceral/diagnóstico , Leucócitos/metabolismo , MicroRNAs/metabolismo , Baço/metabolismo , Animais , Antagomirs/metabolismo , Anticorpos Monoclonais/imunologia , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Cães , Regulação para Baixo , Fator de Transcrição GATA3/metabolismo , Imunidade Celular , Interleucina-12/antagonistas & inibidores , Leishmania infantum/imunologia , Leishmania infantum/fisiologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Leucócitos/citologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Baço/imunologia , Proteínas com Domínio T/metabolismo , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/citologia , Células Th2/imunologia , Células Th2/metabolismo , Regulação para Cima
9.
Stem Cell Res Ther ; 10(1): 393, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847890

RESUMO

AIM: Myocardial infarction (MI) is a severe disease with increased mortality and disability rates, posing heavy economic burden for society. Exosomes were uncovered to mediate intercellular communication after MI. This study aims to explore the effect and mechanism of lncRNA KLF3-AS1 in exosomes secreted by human mesenchymal stem cells (hMSCs) on pyroptosis of cardiomyocytes and MI. METHODS: Exosomes from hMSCs were isolated and identified. Exosomes from hMSCs with transfection of KLF3-AS1 for overexpression were injected into MI rat model or incubated with hypoxia cardiomyocytes. Effect of KLF3-AS1 on MI area, cell viability, apoptosis, and pyroptosis was determined. The relationship among miR-138-5p, KLF3-AS1, and Sirt1 was verified by dual-luciferase reporter assay. Normal cardiomyocytes were transfected with miR-138-5p inhibitor or sh-Sirt1 to clarify whether alteration of miR-138-5p or sh-Sirt1 can regulate the effect of KLF3-AS1 on cardiomyocytes. RESULTS: Exosomes from hMSCs were successfully extracted. Transfection of KLF3-AS1 exosome in rats and incubation with KLF3-AS1 exosome in hypoxia cardiomyocytes both verified that overexpression of KLF3-AS1 in exosomes leads to reduced MI area, decreased cell apoptosis and pyroptosis, and attenuated MI progression. KLF3-AS1 can sponge miR-138-5p to regulate Sirt1 expression. miR-138-5p inhibitor transfection and KLF3-AS1 exosome incubation contribute to attenuated pyroptosis and MI both in vivo and in vitro, while transfection of sh-Sirt1 could reverse the protective effect of exosomal KLF3-AS1 on hypoxia cardiomyocytes. CONCLUSION: LncRNA KLF3-AS1 in exosomes secreted from hMSCs by acting as a ceRNA to sponge miR-138-5p can regulate Sirt1 so as to inhibit cell pyroptosis and attenuate MI progression.


Assuntos
Exossomos/metabolismo , MicroRNAs/metabolismo , Piroptose , RNA Longo não Codificante/metabolismo , Sirtuína 1/metabolismo , Animais , Antagomirs/metabolismo , Apoptose , Hipóxia Celular , Meios de Cultivo Condicionados/farmacologia , Exossomos/transplante , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Piroptose/efeitos dos fármacos , Interferência de RNA , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Ratos , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/genética , Regulação para Cima
10.
Stem Cell Res Ther ; 10(1): 400, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852544

RESUMO

BACKGROUND: Emerging evidence suggests that miR-124 performs important biological functions in neural stem cells (NSCs); it regulates NSC behavior and promotes the differentiation of NSCs into neurons, but the exact molecular mechanism remains unknown. And also, the role of miR-124 during spinal cord injury regeneration is unclear. MATERIALS AND METHODS: In order to explore the function of miR-124 in neural differentiation, the molecular markers (Tuj1, Map2, and GFAP) correlated with the differentiation of NSCs were detected by immunofluorescence staining both in cultured mouse spinal cord progenitor cells (SC-NPCs) and in spinal cord injury (SCI) animal models. The migration ability and apoptosis of cultured SC-NPCs were also evaluated by Transwell migration assay and TUNEL assay. In addition, the relative expression of lnRNA Neat1- and Wnt/ß-catenin signaling-related genes were detected by quantitative real-time PCR. RESULTS: In this study, we revealed that lncRNA Neat1 is involved in regulating Wnt/ß-catenin signaling that is activated by miR-124 in SC-NPCs. LncRNA Neat1 was also found to play an important role in regulating neuronal differentiation, apoptosis, and migration of SC-NPCs. Furthermore, we demonstrated that overexpression of miR-124 resulted in elevated Neat1 expression, accompanied with the functional recovery of locomotion in a mouse model of spinal cord injury. CONCLUSIONS: Our results confirm the therapeutic effectiveness of miR-124 on the functional recovery of injured spinal cord, supporting the rationale and feasibility of miR-124 for spinal cord injury treatment in future clinical therapy. Furthermore, we concluded that the miR-124-Neat1-Wnt/ß-catenin signaling axis is involved in regulating the cell function of SC-NPCs, and this may offer novel therapeutic avenues for future treatment of SCI.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , Animais , Antagomirs/metabolismo , Apoptose , Diferenciação Celular , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Regeneração Nervosa , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Medula Espinal/citologia , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
11.
Cell Physiol Biochem ; 53(6): 910-920, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31769258

RESUMO

BACKGROUND/AIMS: Exposure to heavy metals is today a threat to society. The understanding of the molecular processes related to diseases related to exposure to metals mixture involve changes in the expression of microRNAs. Changes on microRNAs expression may alter several cellular processes, among them, DNA repair inhibition has been described as an essential event leading to the initiation of metal-induced carcinogenesis. METHODS: We evaluate the miR-222 expression in the two-stage transformation Balb/c 3T3 cell assay treated with As-Cd-Pb mixture. RESULTS: We could appreciate that up-regulation of miR-222 reduces the expression both gene and as a protein expression of Rad51c by RT-PCR and immunoblot, respectively. CONCLUSION: Here, we demonstrate that the mixture of As-Cd-Pb at epidemiologically relevant concentrations induces miR-222 up-regulation, which directly negatively regulates Rad51c expression and impairs homologous recombination of DNA during the initiation stage of cell transformation. This inhibition triggers morphological transformation in a murine two-stage Balb/c 3T3 cell assay, suggesting that this small RNA acts as an initiator of the carcinogenesis process.


Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Metais Pesados/farmacologia , MicroRNAs/metabolismo , Rad51 Recombinase/metabolismo , Animais , Antagomirs/metabolismo , Arsênico/química , Células 3T3 BALB , Cádmio/química , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Chumbo/química , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Rad51 Recombinase/genética
12.
Int J Pharm ; 572: 118789, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31726199

RESUMO

The levels of microRNAs (miRNAs) are altered in various diseases including glioblastoma (GBM) and this alteration may have widespread effects on various hallmarks of cancer cells. MiR210 is overexpressed in GBM and functions as an oncogenic miRNA. Anti-miR210 therapy holds great promise but its efficient delivery remains a major challenge. Our work here explores a novel role of Tachyplesin (Tpl), a cell-penetrating antimicrobial peptide, as a nanocarrier for anti-miR210. Tpl electrostatically interacts with anti-miR210 at 1:25 and 1:50 (anti-miR:Tpl) weight ratios to form a complex and efficiently delivers anti-miR210 inside GBM cells cultured as 2D and 3D spheroid model. Treatment of GBM cells with the complex significantly inhibited miR210 levels (~90%), proliferation, migration and spheroid formation ability and induced apoptosis as evident by increased levels of caspase 3/7 and ROS. GBM cells pre-treated with anti-miR210:Tpl complex were also found to be sensitive to TMZ mediated action. Uptake of the complex in GBM cells induced the levels of miR210 targeted tumor suppressor genes, NeuroD2 and HIF3A. Overall, our work reveals a novel and efficient miRNA delivery ability of Tpl in glioma cells, holding a great promise for treatment of GBM and potentially for other cancers.


Assuntos
Antagomirs/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Peptídeos Penetradores de Células/metabolismo , Proteínas de Ligação a DNA/metabolismo , Portadores de Fármacos , Glioblastoma/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Peptídeos Cíclicos/metabolismo , Antagomirs/química , Antagomirs/genética , Antagomirs/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Peptídeos Penetradores de Células/química , Proteínas de Ligação a DNA/química , Composição de Medicamentos , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Peptídeos Cíclicos/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Temozolomida/farmacologia
13.
Cell Biochem Funct ; 37(8): 598-607, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31515847

RESUMO

As a deacetylase relying on NAD, sirtuin 1 (SIRT1) has been proven to inhibit osteoclastogenesis directly by repressing reactive oxygen species (ROS) production and TRPV1 channel stimulation modulated by TNF-α. MicroRNAs do not have coding functions, but they influence the expression of particular genes after transcription. Nevertheless, the current understanding of the impact of SIRT1 on osteoclastogenesis is insufficient. Our research explored whether and how miRNAs contributed to osteoclast differentiation modulated by SIRT1 in vitro. In osteoclastogenesis induced by RANKL in bone marrow-derived macrophages (BMMs), repression of SIRT1 expression and enhancement of miR-506 expression were discovered. Transfection with an miR-506 inhibitor repressed miR-506 concentration in BMMs treated with RANKL. Additional research revealed that BMMs with repressed miR-506 treated with RANKL displayed phenotypes with suppressed osteoclastogenesis, as demonstrated by TRAP staining, reduced function, decreased expression of osteoclast markers and correlated genes, and reduced multinuclear cell quantity. Bioinformatics prediction outcomes and the dual-luciferase reporter test suggested that miR-506 targeted the SIRT1 3'-UTR for silencing. Decreased miR-506 in BMMs induced by RANKL caused SIRT1 upregulation. Additionally, treatment with EX-527 (SIRT1 repressor) or SIRT1 silencing attenuated repression caused by miR-506 depletion in BMMs treated with RANKL. Furthermore, TNF-α was repressed via miR-506 inhibition but was enhanced following EX-527 incubation as well as SIRT1 depletion. TRPV1 channel stimulation and ROS generation, which was related to osteoclastogenesis, were reduced via miR-506 depletion. miR-506 modulated osteoclastogenesis by targeting SIRT1 expression in part through modulation of the TRPV1 channel, ROS production, and TNF-α.


Assuntos
Diferenciação Celular/efeitos dos fármacos , MicroRNAs/metabolismo , Osteogênese/efeitos dos fármacos , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/efeitos dos fármacos , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Células da Medula Óssea/citologia , Células Cultivadas , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Ligante RANK/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/química , Sirtuína 1/genética
14.
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
15.
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 , RNA Circular , Transplante Heterólogo
16.
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
17.
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
18.
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 Circular , RNA Interferente Pequeno/metabolismo , Receptores Acoplados a Proteínas-G/química , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais , Neoplasias Gástricas/metabolismo
19.
Nucleic Acids Res ; 47(15): 7753-7766, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31340025

RESUMO

MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by suppressing mRNA translation and reducing mRNA stability. A miRNA can potentially bind many mRNAs, thereby affecting the expression of oncogenes and tumor suppressor genes as well as the activity of whole pathways. The promise of miRNA therapeutics in cancer is to harness this evolutionarily conserved mechanism for the coordinated regulation of gene expression, and thus restoring a normal cell phenotype. However, the promiscuous binding of miRNAs can provoke unwanted off-target effects, which are usually caused by high-dose single-miRNA treatments. Thus, it is desirable to develop miRNA therapeutics with increased specificity and efficacy. To achieve that, we propose the concept of miRNA cooperativity in order to exert synergistic repression on target genes, thus lowering the required total amount of miRNAs. We first review miRNA therapies in clinical application. Next, we summarize the knowledge on the molecular mechanism and biological function of miRNA cooperativity and discuss its application in cancer therapies. We then propose and discuss a systems biology approach to investigate miRNA cooperativity for the clinical setting. Altogether, we point out the potential of miRNA cooperativity to reduce off-target effects and to complement conventional, targeted, or immune-based therapies for cancer.


Assuntos
Antineoplásicos/uso terapêutico , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias/terapia , RNA Neoplásico/genética , Biologia de Sistemas/métodos , Antagomirs/genética , Antagomirs/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Quimioterapia Adjuvante/métodos , Redes Reguladoras de Genes , Humanos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/agonistas , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/metabolismo , Bibliotecas de Moléculas Pequenas/uso terapêutico , Proteínas Supressoras de Tumor/agonistas , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
20.
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
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