Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cell Death Discov ; 8(1): 364, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974003

RESUMO

Doxorubicin (DOX) is an efficacious and widely used drug for human malignancy treatment, but its clinical application is limited due to side effects, especially cardiotoxicity. Our present study revealed that DOX could induce apoptosis in cardiomyocytes. Herein, we screened the dysregulated long noncoding RNAs (lncRNAs) in DOX-treated cardiomyocytes. Notably, overexpression of lncRNA NONMMUT015745 (lnc5745) could alleviate DOX-induced cardiomyocyte apoptosis both in vitro and in vivo. Conversely, silencing lnc5745 promotes cardiomyocyte apoptosis. Moreover, Rab2A, a direct target of lnc5745, possesses a protective effect in DOX-induced cardiotoxicity once knocked down. Importantly, we verified that the p53-related apoptotic signalling pathway was responsible for the lnc5745-mediated protective role against DOX-induced cardiomyocyte apoptosis. Mechanistically, Rab2A interacts with p53 and phosphorylated p53 on Ser 33 (p53 (Phospho-Ser 33)), promotes p53 phosphorylation, thereby activating the apoptotic pathway. Taken together, our results suggested that lnc5745 protects against DOX-induced cardiomyocyte apoptosis through suppressing Rab2A expression, modifying p53 phosphorylation, thereby regulating p53-related apoptotic signalling pathway. Our findings establish the functional mode of the lnc5745-Rab2A-p53 axis in DOX-induced cardiotoxicity. The development of new strategies targeting the lnc5745-Rab2A-p53 axis could attenuate DOX-induced cardiotoxicity, which is beneficial to its clinical anti-tumour application.

2.
Mol Ther Oncolytics ; 24: 814-833, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35317517

RESUMO

Lung cancer (LC) is a commonly diagnosed cancer with an unsatisfactory prognosis. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that mediate cell-cell communication by transporting various biomacromolecules, such as nucleic acids, proteins, and lipids. Noncoding RNAs (ncRNAs), including microRNAs, circular RNAs, and long noncoding RNAs, are important noncoding transcripts that play critical roles in a variety of physiological and pathological processes, especially in cancer. ncRNAs have been verified to be packaged into EVs and transported between LC cells and stromal cells, regulating multiple LC malignant phenotypes, such as proliferation, migration, invasion, epithelial-mesenchymal transition, metastasis, and treatment resistance. Additionally, EVs can be detected in various body fluids and are associated with the stage, grade, and metastasis of LC. Herein, we summarize the biological characteristics and functions of EV ncRNAs in the biological processes of LC, focusing on their potential to serve as diagnostic and prognostic biomarkers of LC as well as their probable role in the clinical treatment of LC. EV ncRNAs provide a new perspective for understanding the mechanism underlying LC pathogenesis and development, which might benefit numerous LC patients in the future.

3.
Int J Biol Sci ; 17(1): 134-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390839

RESUMO

Autophagy is a conserved catabolic process involving the degradation and recycling of damaged biomacromolecules or organelles through lysosomal-dependent pathways and plays a crucial role in maintaining cell homeostasis. Consequently, abnormal autophagy is associated with multiple diseases, such as infectious diseases, neurodegenerative diseases and cancer. Currently, autophagy is considered to be a dual regulator in cancer, functioning as a suppressor in the early stage while supporting the growth and metastasis of cancer cells in the later stage and may also produce therapeutic resistance. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level by silencing targeted mRNA. MiRNAs have great regulatory potential for several fundamental biological processes, including autophagy. In recent years, an increasing number of studies have linked miRNA dysfunction to the growth, metabolism, migration, metastasis, and responses of cancer cells to therapy. Therefore, the study of autophagy-related miRNAs in cancer will provide insights into cancer biology and lead to the development of novel anti-cancer strategies. In the present review, we summarise the current knowledge of miRNA dysregulation during autophagy in cancer, focusing on the relationship between autophagy and miRNAs, and discuss their involvement in cancer biology and cancer treatment.


Assuntos
Autofagia , MicroRNAs/metabolismo , Neoplasias/metabolismo , Animais , Humanos , Neoplasias/terapia
4.
Cell Biochem Funct ; 35(6): 334-338, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28845525

RESUMO

Recent evidence suggests that adventitial fibroblasts (AFs) are crucially implicated in atherosclerosis. However, the mechanisms by which AFs are dysfunctional and contribute to atherosclerosis remain unclear. This study aimed to investigate the role of regulator of G-protein signalling 3 (RGS3) in the regulation of AFs using apoE knockout mouse as the model. Pathological changes in aortic arteries of apoE knockout mice fed with hyperlipid diet were examined by Movat staining. The expression of RGS3, α-SMA, TGF-ß1, Smad2, and Smad3 in the adventitia was detected by immunohistochemistry. Adventitial fibroblasts were isolated from aortic arteries of apoE knockout mice and infected with RGS3 overexpression lentivirus or empty lentivirus. The expression of RGS3, α-SMA, TGF-ß1, Smad2, and Smad3 in AFs was detected by real-time polymerase chain reaction and Western blot analysis. We found that hyperlipidic diet caused significant aortic intima thickening and atherosclerotic plaques in 15-week-old apoE knockout mice. Compared to wild-type mice, RGS3 expression was lower while α-SMA, TGF-ß1, Smad2, and Smad3 expression was higher in the adventitia of apoE knockout mice. In addition, lentivirus mediated overexpression of RGS3 caused decreased expression of α-SMA, TGF-ß1, Smad2, and Smad3 in AFs derived from apoE(-/-) mice. In conclusion, these results suggest that RGS3 may provide protection against pathological changes of AFs and the development of atherosclerosis by inhibiting TGF-ß1/Smad signalling. RGS3 may be a potential therapeutic target for atherosclerosis.


Assuntos
Proteínas RGS/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Aorta/citologia , Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Células Cultivadas , Dieta Hiperlipídica , Regulação para Baixo , Fibroblastos/citologia , Fibroblastos/metabolismo , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Imuno-Histoquímica , Lentivirus/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas RGS/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Proteína Smad2/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética
5.
Pharmazie ; 71(2): 94-100, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27004374

RESUMO

The vascular remodeling process plays an important role in the pathology of hypoxia-induced pulmonary hypertension, and it includes cell proliferation, cell motility, cell synthesis and collagen coagulation. Due to their proliferation and synthesis ability, the adventitial fibroblasts are thought to be critical in the vascular remodeling process initiated in response to hypoxia. However, the factors driving hypoxia-induced fibroblast proliferation and synthesis have yet to be elucidated, and the treatment regimens to treat hypoxia remain ineffective. As forthis study, its purpose was to examine the effects exerted by SB-431542, a small-molecule antagonist of transforming growth factor-ß-receptor, on the proliferation, synthesis and collagen coagulation in cultured adventitial fibroblasts. Another aim of this study was to assess the inhibitory ability of SB-431542 on pulmonary vascular remodeling in chronic hypoxia in vivo.The cell morphology and proliferation of cultured adventitial fibroblasts was assessed by laser confocal microscopy and the MTT assay, respectively. Additionally, collagen synthesis was determined by hydroxyproline chromatography, while the expression of cytokines in adventitial fibroblasts and lung tissues was evaluated by immunohistochemical and reverse transcription PCR analyses. The results indicated that the exposure of cultured fibroblasts to 1% oxygen led to the up regulation of cell proliferation, cell synthesis. In addition, increased expression of cytokines and collagen was detected in vivo in the pulmonary artery adventitia of rats exposed to chronic hypoxia. Conversely, SB-431542 inhibited fibroblast proliferation and synthesis in the process of hypoxia-induced pulmonary hypertension (P < 0.01). Thus, the results suggested that by reducing cell proliferation, cell synthesis of vascular adventitia, small molecule inhibitors of the TGF-ß1 receptors may offer a novel therapy for pulmonary hypertension.


Assuntos
Benzamidas/farmacologia , Dioxóis/farmacologia , Fibroblastos/efeitos dos fármacos , Hipóxia/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Artéria Pulmonar/patologia , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Actinas/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno/biossíntese , Citocinas/biossíntese , Regulação para Baixo/efeitos dos fármacos , Hidroxiprolina/metabolismo , Masculino , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 1 da Matriz/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/biossíntese , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I
6.
J Transl Med ; 13: 38, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25628043

RESUMO

BACKGROUND: Reactive oxide species (ROS) derived from NADPH oxidases is involved in atherosclerosis. However, as a key component of NADPH oxidase, how p47phox regulates NADPH oxidases activity, ROS production and adventitial fibroblasts (AFs) function remains unclear. METHODS: p47phox in aortic arteries of apoE(-/-) mice fed with hyperlipid diet was detected by immunohistochemistry. NADPH oxidase activity, superoxide anion (O2(-)) generation and p47phox expression were analyzed in primary AFs treated by diphenyleneiodonium (DPI). The proliferation and migration of AFs were also analyzed. RESULTS: p47phox expression was low in the aortic adventitia but high in the site of intimal injury with continuous hyperlipidic diet. Compared to AFs from wild-type mice, AFs derived from apoE(-/-) mice exhibited elevated NADPH oxidase activity, O2(-) production and higher mRNA and protein levels of p47phox, correlated with increased capability of proliferation and migration. DPI inhibited NADPH oxidase activity and AFs proliferation and migration in a dose-dependent manner. In addition, siRNA mediated knockdown of p47phox attenuated the proliferation and migration of AFs derived from apoE(-/-) mice. CONCLUSION: p47phox plays a critical role in the regulation of adventitial fibroblast proliferation and migration and may be a new therapeutic target for neointimal hyperplasia.


Assuntos
Apolipoproteínas E/fisiologia , Movimento Celular/genética , Proliferação de Células/genética , NADPH Oxidases/genética , RNA Interferente Pequeno/genética , Animais , Apolipoproteínas E/genética , Sequência de Bases , Fibroblastos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...