RESUMO
Long non-coding RNAs (lncRNAs) have obtained growing attention due to their potential effects as novel regulators in various tumors. This study aimed to investigate the expression and roles of lncRNA LINC01139 (LINC01139) in the progression of hepatocellular carcinoma (HCC). We found that LINC01139 was over-expressed in HCC specimens and cell lines, and its upregulation was observed to be associated with advanced TNM stage, lymph node metastasis and poor clinical prognosis of HCC patients. Multivariate analyses confirmed that LINC01139 expression was an independent poor prognostic factor for HCC patients. Functionally, the knockdown of LINC01139 suppressed cell proliferation, clone formation and metastasis of HCC cells. Moreover, luciferase assays and rescue experiments revealed that LINC01139/miR-30/MYBL2 established the ceRNA network involved in the modulation of cell proliferation and metastasis of HCC cells. Overall, LINC01139 may exhibit an oncogenic function in HCC via acting as a sponge for miR-30 to upregulate MYBL2, and may serve as a potential therapeutic target and a prognostic biomarker for HCC patients.
Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Progressão da Doença , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transativadores/genética , Regulação para Cima/genética , Sequência de Bases , Ligação Competitiva , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , RNA Longo não Codificante/genética , Transativadores/metabolismoRESUMO
OBJECTIVE: KN motif and ankyrin repeat domains 2 (KANK2) may inhibit the activation of (NF-kappaB) p65, which plays a role in myocardial injury. Thus, our study aims to discover the effect of KANK2 on myocardial infarction (MI) induced by ligating the left anterior descending coronary artery (LAD) through regulating NF-κB p65 in vivo. METHODS: MI rats underwent LAD ligation were administered with intramyocardial injections of KANK2/Control activation plasmids. Six weeks after MI, pressure-volume (P/V) loops was used to investigate the cardiac function of rats, then the following detections were performed, including TTC staining, HE staining, immunofluorescence, Masson' s trichrome staining, ELISA assay, TUNEL staining, immunohistochemistry, qRT-PCR and Western blotting. RESULTS: MI rats decreased in maximum pressure (pmax), ejection fraction (EF%), peak rate of pressure rise (dpdtmax) and decline (-dpdtmax) with increased end diastolic pressure (EDP), which was partially reversed by KANK2 overexpression. Besides, KANK2 CRISPR activation plasmids reduced infarct size with less collagen fiber proliferation and neutrophil infiltration in infarct tissues, as well as suppressed pro-inflammatory factors expressions in MI rats. Moreover, injection of KANK2 activation plasmid decreased collagen deposition, aggravated cardiomyocyte apoptosis, enhanced the capillary density, and increased the expressions of VEGF and bFGF in the infarct and peri-infarct regions of MI rats. KANK2 lowered myocardial NF-κB p65 expression in MI rats. CONCLUSION: KANK2 may play its therapeutic role in MI through improving cardiac function, decreasing myocardial collagen deposition, reducing cardiomyocyte apoptosis, and increasing angiogenesis, which might be associated with the reduction of NF-κB p65 expression.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Infarto do Miocárdio/metabolismo , Fator de Transcrição RelA/antagonistas & inibidores , Animais , Apoptose/genética , Capilares/crescimento & desenvolvimento , Colágeno/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Fator 2 de Crescimento de Fibroblastos/metabolismo , Infarto do Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular EsquerdaRESUMO
The aim of the present study was to investigate the potential role of matrix metalloproteinase7 (MMP7) and apoptosisassociated genes [TIMP metallopeptidase inhibitor 2(TIMP2), BCL2 associated X, apoptosis regulator (BAX) and BCL2, apoptosis regulator (BCL2)] in the pathogenesis of atrial fibrillation (AF) in a Beagle dog model. A total of 20 adult male Beagle dogs were randomly assigned into the AF group (n=10; Beagle dogs were treated by Burst stimulation to induce AF) and the control group (n=10; healthy Beagle dogs). Echocardiography and Mallory staining were used to determine cardiac function and degree of atrial fibrosis, respectively. Reverse transcriptionquantitative polymerase chain reaction and western blotting were performed to determine collagen type 1 (Col I), MMP7, TIMP2, BAX and BCL2 mRNA and protein expression levels. Compared with the control group, the AF group presented increased degree of atrial fibrosis and level of Col I expression, elevated MMP7 and BAX expression levels, but decreased TIMP2 and BCL2 expression levels. Correlation analysis demonstrated that MMP7 and BAX protein expression levels were negatively correlated with left ventricular ejection fraction (LVEF), but positively correlated with the degree of atrial fibrosis. Negative correlation was observed between TIMP2 and BCL2 protein expression levels and degree of atrial fibrosis. In addition, a positive correlation between TIMP2 and BCL2 protein expression levels and LEVF was observed. These results demonstrate that MMP7 and BAX were highly expressed, while TIMP2 and BCL2 were downregulated in a Beagle dog model of AF, indicating that MMP7 and apoptosisassociated genes (TIMP2, BAX and BCL2) may be associated with the pathogenesis of AF.