RESUMO
Hepatoblastoma is the most common malignant hepatic tumour type with hypervascularity in early childhood. In recent decades, emerging evidence has proven that long noncoding RNAs (lncRNAs) serve an important oncogenic role in the pathogenesis of hepatoblastoma. However, the underlying mechanism of lncRNA taurine upregulated 1 (TUG1) in the angiogenesis of hepatoblastoma remains unknown. The expression patterns of TUG1 and microRNA (miR)2045p were detected in hepatoblastoma tissues and cell lines via reverse transcriptionquantitative PCR and were analysed using a Pearson's correlation test. A tube formation assay was performed using human umbilical vein endothelial cells to assess the vasculogenic activity of treated HuH6 cells. ELISA was used to detect the level of the secretory proangiogenic factor VEGFA in the culture media of HuH6 cells. A dual luciferase reporter assay was performed to validate the binding relationships of TUG1/miR2045p and miR2045p/Janus kinase 2 (JAK2). Moreover, western blotting was conducted to measure the protein expression levels of VEGFA, phosphorylated (p)JAK2, JAK2, pSTAT3 and STAT3. It was identified that TUG1 was upregulated, while miR2045p was downregulated in hepatoblastoma tissues and cells. TUG1 knockdown inhibited angiogenesis induced by hepatoblastoma cells. Furthermore, miR2045p was identified as a target of TUG1. The results demonstrated that TUG1 attenuated the inhibitory effect of miR2045p on the JAK2/STAT3 pathway and promoted angiogenesis in hepatoblastoma cells. In summary, TUG1 was upregulated in hepatoblastoma and suppressed miR2045p, thereby activating the downstream signalling pathway of JAK2/STAT3 to facilitate angiogenesis. The present findings will provide novel targets for the treatment of hepatoblastoma.
Assuntos
Hepatoblastoma/genética , Janus Quinase 2/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Pré-Escolar , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Hepatoblastoma/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lactente , Neoplasias Hepáticas/metabolismo , Masculino , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Regulação para Cima/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.
Assuntos
Hepatoblastoma/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Fator A de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Novel auxiliary truncated unscented Kalman filtering (ATUKF) is proposed for bearings-only maneuvering target tracking in this paper. In the proposed algorithm, to deal with arbitrary changes in motion models, a modified prior probability density function (PDF) is derived based on some auxiliary target characteristics and current measurements. Then, the modified prior PDF is approximated as a Gaussian density by using the statistical linear regression (SLR) to estimate the mean and covariance. In order to track bearings-only maneuvering target, the posterior PDF is jointly estimated based on the prior probability density function and the modified prior probability density function, and a practical algorithm is developed. Finally, compared with other nonlinear filtering approaches, the experimental results of the proposed algorithm show a significant improvement for both the univariate nonstationary growth model (UNGM) case and bearings-only target tracking case.
RESUMO
Tracking the target that maneuvers at a variable turn rate is a challenging problem. The traditional solution for this problem is the use of the switching multiple models technique, which includes several dynamic models with different turn rates for matching the motion mode of the target at each point in time. However, the actual motion mode of a target at any time may be different from all of the dynamic models, because these models are usually limited. To address this problem, we establish a formula for estimating the turn rate of a maneuvering target. By applying the estimation method of the turn rate to the multi-target Bayes (MB) filter, we develop a MB filter with an adaptive estimation of the turn rate, in order to track multiple maneuvering targets. Simulation results indicate that the MB filter with an adaptive estimation of the turn rate, is better than the existing filter at tracking the target that maneuvers at a variable turn rate.
RESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of leukemia patients can improve overall survival and disease-free survival, and reduce relapse. Although the allo-HSCT is more widely used in the treatment of leukemia, but the graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infections are the common complications, and are the major cause of mortality for patients following allo-HSCT. Previous studies showed that there might be a mutual promotive relationship between GVHD and CMV infection, but the clear relationship remained to be elucidated. The relationship of GVHD and CMV has been the focus of clinical research. Recently, a great progress has been made on researches of the relationship and its mechanism between GVHD and CMV infection. In this article, the relationship and its mechanism between GVHD and CMV infection after allo-HSCT are reviewed.