BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
Astragalus extract Astragalus polysaccharide(APS),a natural extract,has been demonstrated to exert inhibitory effects on the development of various tumors by modulating microRNA(miRNA).However,the precise regulatory m...Astragalus extract Astragalus polysaccharide(APS),a natural extract,has been demonstrated to exert inhibitory effects on the development of various tumors by modulating microRNA(miRNA).However,the precise regulatory mechanism of miRNA-223(miR-223)in brain glioma cells remains unclear.This study aimed to investigate the inhibitory effect of Astragalus extract APS on brain glioma cells through the miR-223/FBXW7 signaling pathway and its potential mechanism.Using the TargetScan tool,we predicted the binding between miR-223 and FBXW7 and confirmed this binding relationship through dual luciferase assay.We compared the expression of miR-223 and FBXW7 in glioma and adjacent tissues and followed up the prognosis.U87 cells were subjected to APS treatment or were transfected with small interfering RNA(siRNA)of miR-223 mimics to examine the effects of these treatments on cell proliferation,apoptosis,and FBXW7 expression.Our results demonstrated that miR-223 directly bound to FBXW7,as confirmed by dual luciferase assay.Moreover,the mRNA expression of miR-223 in glioma tissues was higher than that in paracancerous tissues,while the mRNA and protein levels of FBXW7 in glioma tissues were lower than those in paracancerous tissues.In addition,we observed a negative correlation between the expression of miR-223 and FBXW7(P<0.05).APS significantly inhibited the proliferation and invasion of U87 cells,suppressed the expression of miR-223,and promoted the expression of FBXW7(P<0.05).Transfection of miR-223 mimic into cells reversed the inhibition of miR-223 and the increase of FBXW7 induced by APS(P<0.05).Therefore,our findings suggested that APS might inhibit the proliferation and invasion of the glioma cell line U87 through the miR-223/FBXW7 signaling pathway.展开更多
目的:探讨Fbxw7在肝癌中的表达及其与肝癌细胞增殖能力的相关性。方法:收集40例肝细胞癌组织及对应的癌旁组织,运用RT-PCR、免疫组化技术检测Fbxw7在肝癌及对应癌旁组织中的表达情况;real time RT-PCR技术检测正常肝细胞株LO2、肝癌细胞...目的:探讨Fbxw7在肝癌中的表达及其与肝癌细胞增殖能力的相关性。方法:收集40例肝细胞癌组织及对应的癌旁组织,运用RT-PCR、免疫组化技术检测Fbxw7在肝癌及对应癌旁组织中的表达情况;real time RT-PCR技术检测正常肝细胞株LO2、肝癌细胞株Hep3B和SMMC-7721中Fbxw7 mRNA的表达水平;平板克隆形成实验与裸鼠皮下成瘤实验检测不同Fbxw7 mRNA表达水平的细胞株体内外增殖能力。结果:Fbxw7 mRNA及蛋白在肝癌组织中表达水平显著低于对应癌旁组织(P<0.05);Fbxw7蛋白低表达与高Edmonson分级和高TNM分期具有显著的相关性(P<0.05);正常肝细胞株LO2中Fbxw7 mRNA的表达水平显著高于肝癌细胞株Hep3B和SMMC-7721(P<0.05);Fbxw7表达较低的细胞株形成的克隆数较多,且裸鼠皮下成瘤体积较大,结果均具有统计学差异(P<0.05)。结论:Fbxw7低表达与肝癌的恶性临床病理特征相关,并与肝癌细胞增殖能力相关。展开更多
背景:F-Box和WD40蛋白7(F-Box and WD40 domain protein 7,FBXW7)是E3泛素连接酶复合物的组份,控制NOTCH1,c-MYC和Cyclin E等多种蛋白的降解。目的:研究成人T细胞性急性淋巴细胞白血病(T-ALL)中FBXW7基因突变。方法:通过对54例成人T-AL...背景:F-Box和WD40蛋白7(F-Box and WD40 domain protein 7,FBXW7)是E3泛素连接酶复合物的组份,控制NOTCH1,c-MYC和Cyclin E等多种蛋白的降解。目的:研究成人T细胞性急性淋巴细胞白血病(T-ALL)中FBXW7基因突变。方法:通过对54例成人T-ALL患者FBXW7外显子5-12进行扩增、克隆和测序,分析FBXW7突变的发生率、突变位点和类型、与NOTCH1突变的相关性及其临床预后意义。结果:本组成人T-ALL中FBXW7突变率11.1%,共发现4种点突变(R465H,R465L,R479P和R505C)和1个插入/缺失突变,FBXW7突变全部位于WD40结构域。研究还发现,FBXW7突变患者中83.3%同时存在NOTCH1突变,与FBXW7突变并存的NOTCH1突变均发生于HD结构域,包括点突变(L1574P,L1596H和L1600P),和缺失/插入突变。此外,研究还显示,FBXW7单独突变组患者的总生存时间比无突变组延长(P=0.049)。结论:FBXW7突变可能在NOTCH1介导的TALL发病机制有重要作用。展开更多
F框/WD-40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)基因,又称FBW7或h CDC4,是泛素蛋白酶体降解途径的重要识别因子之一,参与靶向降解多种癌蛋白,进而调控恶性肿瘤的发生发展过程,目前已被认为是一种抑癌基因。本综述着重探索FB...F框/WD-40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)基因,又称FBW7或h CDC4,是泛素蛋白酶体降解途径的重要识别因子之一,参与靶向降解多种癌蛋白,进而调控恶性肿瘤的发生发展过程,目前已被认为是一种抑癌基因。本综述着重探索FBXW7基因在恶性肿瘤发生发展中的作用,旨在为肿瘤治疗提供新的切入点和诊疗思路。展开更多
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.
基金National Key Research and Development Project(Grant No.2016YFC1101503)。
文摘Astragalus extract Astragalus polysaccharide(APS),a natural extract,has been demonstrated to exert inhibitory effects on the development of various tumors by modulating microRNA(miRNA).However,the precise regulatory mechanism of miRNA-223(miR-223)in brain glioma cells remains unclear.This study aimed to investigate the inhibitory effect of Astragalus extract APS on brain glioma cells through the miR-223/FBXW7 signaling pathway and its potential mechanism.Using the TargetScan tool,we predicted the binding between miR-223 and FBXW7 and confirmed this binding relationship through dual luciferase assay.We compared the expression of miR-223 and FBXW7 in glioma and adjacent tissues and followed up the prognosis.U87 cells were subjected to APS treatment or were transfected with small interfering RNA(siRNA)of miR-223 mimics to examine the effects of these treatments on cell proliferation,apoptosis,and FBXW7 expression.Our results demonstrated that miR-223 directly bound to FBXW7,as confirmed by dual luciferase assay.Moreover,the mRNA expression of miR-223 in glioma tissues was higher than that in paracancerous tissues,while the mRNA and protein levels of FBXW7 in glioma tissues were lower than those in paracancerous tissues.In addition,we observed a negative correlation between the expression of miR-223 and FBXW7(P<0.05).APS significantly inhibited the proliferation and invasion of U87 cells,suppressed the expression of miR-223,and promoted the expression of FBXW7(P<0.05).Transfection of miR-223 mimic into cells reversed the inhibition of miR-223 and the increase of FBXW7 induced by APS(P<0.05).Therefore,our findings suggested that APS might inhibit the proliferation and invasion of the glioma cell line U87 through the miR-223/FBXW7 signaling pathway.
文摘背景:F-Box和WD40蛋白7(F-Box and WD40 domain protein 7,FBXW7)是E3泛素连接酶复合物的组份,控制NOTCH1,c-MYC和Cyclin E等多种蛋白的降解。目的:研究成人T细胞性急性淋巴细胞白血病(T-ALL)中FBXW7基因突变。方法:通过对54例成人T-ALL患者FBXW7外显子5-12进行扩增、克隆和测序,分析FBXW7突变的发生率、突变位点和类型、与NOTCH1突变的相关性及其临床预后意义。结果:本组成人T-ALL中FBXW7突变率11.1%,共发现4种点突变(R465H,R465L,R479P和R505C)和1个插入/缺失突变,FBXW7突变全部位于WD40结构域。研究还发现,FBXW7突变患者中83.3%同时存在NOTCH1突变,与FBXW7突变并存的NOTCH1突变均发生于HD结构域,包括点突变(L1574P,L1596H和L1600P),和缺失/插入突变。此外,研究还显示,FBXW7单独突变组患者的总生存时间比无突变组延长(P=0.049)。结论:FBXW7突变可能在NOTCH1介导的TALL发病机制有重要作用。
文摘F框/WD-40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)基因,又称FBW7或h CDC4,是泛素蛋白酶体降解途径的重要识别因子之一,参与靶向降解多种癌蛋白,进而调控恶性肿瘤的发生发展过程,目前已被认为是一种抑癌基因。本综述着重探索FBXW7基因在恶性肿瘤发生发展中的作用,旨在为肿瘤治疗提供新的切入点和诊疗思路。
