远端上游元件结合蛋白1(far upstream element binding protein 1,FUBP1)通过特异性结合远端上游元件(upstream element,FUSE)调控原癌基因c-Myc的转录。FUBP家族包括FUBP1、FUBP2、FUBP3及FUBP4,其序列具有高度同源性,但功能各不相同。...远端上游元件结合蛋白1(far upstream element binding protein 1,FUBP1)通过特异性结合远端上游元件(upstream element,FUSE)调控原癌基因c-Myc的转录。FUBP家族包括FUBP1、FUBP2、FUBP3及FUBP4,其序列具有高度同源性,但功能各不相同。FUBP1蛋白由3个结构域构成,具有两亲性螺旋结构的N端、富含酪氨酸的C端以及1个DNA结合区域。生理状态下,FUBP1蛋白定位于细胞核。除了调控c-Myc转录外,FUBP1还可结合RNA,参与调控mRNA稳定性、病毒复制及RNA的剪接。展开更多
Background:Pancreatic cancer(PC)is a highly deadly malignancy with few effective therapies.We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6(SNHG6)plays in PC cells by targeting far ...Background:Pancreatic cancer(PC)is a highly deadly malignancy with few effective therapies.We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6(SNHG6)plays in PC cells by targeting far upstream element binding protein 1(FUBP1)via microRNA-26a-5p(miR-26a-5p).Methods::SNHG6 expression was predicted by bioinformatics,followed by verification via reverse transcription quantitative polymerase chain reaction.Then,the interactions among SNHG6,miR-26a-5p,and FUBP1 were detected through online software analysis,dual luciferase reporter assay and RNA pull-down.After that,cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6,miR-26a-5p,and FUBP1 and their roles in PC cells.Finally,the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice.A t-test,one-way and two-way analysis of variance were used for data analysis.Results::Compared with that in normal tissues,SNHG6 was highly expressed in PC tissues(1.00±0.05 vs.1.56±0.06,t=16.03,P<0.001).Compared with that in human pancreatic duct epithelial cells(HPDE6-C7),SNHG6 showed the highest expression in PANC-1 cells(1.00±0.06 vs.3.87±0.13,t=34.72,P<0.001)and the lowest expression in human pancreatic cancer cells(MIAPaCa-2)(1.00±0.06 vs.1.41±0.07,t=7.70,P=0.0015).Compared with the levels in the si-negative control group,SNHG6(0.97±0.05 vs.0.21±0.06,t=16.85,P<0.001),N-cadherin(0.74±0.05 vs.0.41±0.04,t=8.93,P<0.001),Vimentin(0.55±0.04 vs.0.25±0.03,t=10.39,P<0.001),andβ-catenin(0.62±0.05 vs.0.32±0.03,t=8.91,P<0.001)were decreased,while E-cadherin(0.65±0.06 vs.1.36±0.07,t=13.34,P<0.001)was increased after SNHG6 knockdown or miR-26a-5p overexpression,accompanied by inhibited cell proliferation,migration,and invasion.SNHG6 overexpression exerted the opposite effects.SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p.Silencing SNHG6 blocked the growth of PC in vivo.Conclusion::Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p,thus providing further supporting evidence for its use in PC treatment.展开更多
文摘远端上游元件结合蛋白1(far upstream element binding protein 1,FUBP1)通过特异性结合远端上游元件(upstream element,FUSE)调控原癌基因c-Myc的转录。FUBP家族包括FUBP1、FUBP2、FUBP3及FUBP4,其序列具有高度同源性,但功能各不相同。FUBP1蛋白由3个结构域构成,具有两亲性螺旋结构的N端、富含酪氨酸的C端以及1个DNA结合区域。生理状态下,FUBP1蛋白定位于细胞核。除了调控c-Myc转录外,FUBP1还可结合RNA,参与调控mRNA稳定性、病毒复制及RNA的剪接。
基金This study was supported by a grant from the Shanghai University of Medicine&Health Sciences Seed Foundation(No.SFP-18-22-15-002).
文摘Background:Pancreatic cancer(PC)is a highly deadly malignancy with few effective therapies.We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6(SNHG6)plays in PC cells by targeting far upstream element binding protein 1(FUBP1)via microRNA-26a-5p(miR-26a-5p).Methods::SNHG6 expression was predicted by bioinformatics,followed by verification via reverse transcription quantitative polymerase chain reaction.Then,the interactions among SNHG6,miR-26a-5p,and FUBP1 were detected through online software analysis,dual luciferase reporter assay and RNA pull-down.After that,cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6,miR-26a-5p,and FUBP1 and their roles in PC cells.Finally,the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice.A t-test,one-way and two-way analysis of variance were used for data analysis.Results::Compared with that in normal tissues,SNHG6 was highly expressed in PC tissues(1.00±0.05 vs.1.56±0.06,t=16.03,P<0.001).Compared with that in human pancreatic duct epithelial cells(HPDE6-C7),SNHG6 showed the highest expression in PANC-1 cells(1.00±0.06 vs.3.87±0.13,t=34.72,P<0.001)and the lowest expression in human pancreatic cancer cells(MIAPaCa-2)(1.00±0.06 vs.1.41±0.07,t=7.70,P=0.0015).Compared with the levels in the si-negative control group,SNHG6(0.97±0.05 vs.0.21±0.06,t=16.85,P<0.001),N-cadherin(0.74±0.05 vs.0.41±0.04,t=8.93,P<0.001),Vimentin(0.55±0.04 vs.0.25±0.03,t=10.39,P<0.001),andβ-catenin(0.62±0.05 vs.0.32±0.03,t=8.91,P<0.001)were decreased,while E-cadherin(0.65±0.06 vs.1.36±0.07,t=13.34,P<0.001)was increased after SNHG6 knockdown or miR-26a-5p overexpression,accompanied by inhibited cell proliferation,migration,and invasion.SNHG6 overexpression exerted the opposite effects.SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p.Silencing SNHG6 blocked the growth of PC in vivo.Conclusion::Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p,thus providing further supporting evidence for its use in PC treatment.
