RESUMO
Chemoresistance is a major obstacle faced by oesophageal cancer patients and is synonymous with a poor prognosis. MCL1 is a pivotal member of the anti-apoptotic Bcl-2 protein family, which has been found to play an important role in cell survival, proliferation, differentiation and chemoresistance. Thus, it might be an ideal target for treating oesophageal cancer patients. Although it is known that MCL1 is degraded via the ubiquitin-proteasome system, the deubiquitylating enzyme (DUB) responsible for stabilizing MCL1 remains elusive to date. Herein, we demonstrate that Ubiquitin-Specific Protease 20 (USP20) is a novel regulator of the apoptotic signaling pathway. Moreover, USP20 could regulate the deubiquitination of MCL1 to, in turn, regulate its stability. Increased expression of USP20 was correlated with increased levels of MCL1 protein in human patient samples. In addition, depletion of USP20 could increase the polyubiquitination of MCL1, thereby increasing the conversion rate of MCL1 and the sensitivity of cells to chemotherapy. Overall, our findings indicate that the USP20-MCL1 axis might play a key role in the apoptotic signaling pathway.
Assuntos
Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Proteína de Sequência 1 de Leucemia de Células Mieloides/química , Ubiquitina Tiolesterase/metabolismo , Ubiquitina/metabolismo , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Células HEK293 , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Complexo de Endopeptidases do Proteassoma , Estabilidade Proteica , Transdução de Sinais , Sorafenibe/farmacologia , Células Tumorais Cultivadas , Ubiquitina Tiolesterase/genética , UbiquitinaçãoRESUMO
Emerging evidences show RNA back-splicing produces a new type of noncoding RNA, namely circular RNA (circRNA). Many reports demonstrate that circRNA circHIPK3 exerts oncogenic or anti-tumor roles in different cancers, such as ovarian cancer, bladder cancer, osteosarcoma, colorectal cancer and liver cancer. However, no study about circHIPK3 function in glioma exists until today. In this study, we showed that circHIPK3 was upregulated in glioma tissues. Elevated level of circHIPK3 was linked to poor prognosis. Functional investigation indicated that circHIPK3 promotes glioma cell proliferation and invasion, and tumor propagation in vivo. Furthermore, miR-654 was identified as a target of circHIPK3 while IGF2BP3 was targeted by miR-654. CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. Finally, CCK8 and transwell assays illustrated that IGF2BP3 overexpression could reverse the effects of IGF2BP3 depletion. Altogether, our findings demonstrated that circHIPK3 contributes to glioma progression through targeting miR-654 from IGF2BP3 and implies circHIPK3 might be a potential target for glioma therapy.
Assuntos
Biomarcadores Tumorais/metabolismo , Glioma/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Células Cultivadas , Glioma/genética , Glioma/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/genética , RNA/análise , RNA/genética , RNA Circular , Transdução de SinaisRESUMO
Numerous long noncoding RNAs (lncRNAs) are reported to be dysregulated in glioma. However, how lncRNA participates in the process of glioma development and progression still remains elusive. Here, we identified a novel lncRNA LOC728196 highly expressed in glioma tissues. LOC728196 high expression predicts low survival rate in patients. Our data proved that LOC728196 knockdown repressed cellular growth, migration and invasion in vitro. Silencing LOC728196 led to impaired growth of glioma in vivo. Mechanistic studies further demonstrated that LOC728196 acts as the sponge for miR-513c to upregulate TCF7 expression. We observed a reciprocal inhibition between LOC728196 and miR-513c. Rescue assay showed that either inhibition of miR-513c or TCF7 overexpression restored the abilities of proliferation, migration and invasion in LOC728196-silenced glioma cells. Taken together, our study provides a comprehensive investigation on the role of LOC728196 in glioma progression and contributes to understanding the vital role of competing endogenous RNA (ceRNA).
Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator 1 de Transcrição de Linfócitos T/genética , Regiões 3' não Traduzidas , Animais , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico , Análise de Sobrevida , Regulação para CimaRESUMO
We report a facile and robust synthesis of ZnCdS core/shell quantum dots (QDs) with thick CdxZn1-xS (x = constant) uniform alloys as an intermediate shell which can provide effective confinement of excitons within the ZnCdS cores and ultrathin ZnS outermost shell to improve the stability by epitaxial growth at a relatively high temperature. The resulting nearly monodisperse ZnCdS/CdxZn1-xS/ZnS core/shell QDs have high photoluminescence quantum yield (near to 100%) and high color purity (full width at half maximum (FWHM) < 18 nm). More importantly, the ZnCdS/CdxZn1-xS/ZnS core/shell QDs have good chemical/photochemical stability and more efficient carrier transport performance compared with ZnCdS/ZnS core/shell QDs. Two types of QDs of ZnCdS/ZnS and ZnCdS/CdxZn1-xS/ZnS were incorporated into the solution-processed hybrid QD-based light-emitting device structure as the emissive layer. We find that the presence of the CdxZn1-xS shell makes a profound impact on device performances such as the external quantum efficiency and current efficiency. The corresponding light-emitting diodes exhibited a high EQE exceeding 18%, a peak current efficiency of 3.4 cd A-1 and low efficiency roll-off. Such excellent results of ZnCdS/CdxZn1-xS/ZnS-based QLEDs are likely attributable to the QD's high PL QY and very thin ZnS outermost shell which did not sacrifice the charge injection efficiency in QLEDs.