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作 者:Chu-Xiang Wang Feng Liu Yi Wang
机构地区:[1]Department of Anorectal Surgery,The Affiliated Hospital of Dalian Medical University,Dalian 116000,Liaoning Province,China [2]Department of Scientific Research,Beijing Fresta Technologies Co,Ltd.,Beijing 100176,China [3]Department of VIP Medical Services,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China
出 处:《World Journal of Gastrointestinal Oncology》2024年第7期3241-3255,共15页世界胃肠肿瘤学杂志(英文)
摘 要:BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dictates that is essential.METHODS Through Gene Expression Profiling Interactive Analysis,we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues.For detecting the mRNA expression of RBM5,quantitative real time-polymerase chain reaction was performed.Protein expression levels of RBM5,hexokinase 2,lactate dehydrogenase A,phosphatase and tensin homolog(PTEN),phosphoinositide 3-kinase(PI3K),phosphorylated-protein kinase B(p-AKT),and AKT were determined via Western blot.Functionally,cell counting kit-8 and 5-ethynyl-2’-deoxyuridine(EDU)assay were performed to evaluate proliferation of CRC cells.Invasiveness and migration of CRC cells were evaluated through conducting transwell assays.Glucose consumption,lactate production and adenosinetriphosphate(ATP)production were measured through a glucose assay kit,a lactate assay kit and an ATP production assay kit,respectively.Besides,RNA immunoprecipitation assay,half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN.To establish a xenotypic tumor mice,CRC cells were subcutaneously injected into the right flank of each mouse.Protein expression of RBM5,Ki67,and PTEN in tumor tissues was examined using immunohistochemistry staining.Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.RESULTS We discovered down-regulation of RBM5 expression in CRC tissues and cells.RBM5 overexpression repressed proliferation,migration and invasion of CRC cells.Meantime,RBM5 impaired glycolysis in CRC cells,presenting as decreased glucose consumption,decreased lactate production and decreased ATP production.Besides,RBM5 bound to PTEN mRNA to stabilize its expression.PTEN expression was positively regulated by RBM5 in CRC cells.The protein levels of PI3K and p-AKT were sign
关 键 词:Colorectal cancer RNA binding motif 5 Phosphatase and tensin homolo Phosphoinositide 3-kinase/anti-protein kinase GLYCOLYSIS
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