[目的]探讨miR-330-5p/PTBP1/CTTN轴调控结肠癌细胞凋亡的潜在机制。[方法]纳入接受根治性结肠切除术的结肠癌患者113例,分析miR-330-5p在结肠癌组织和癌旁组织中的表达水平以及其对总生存率的影响。[结果]miR-330-5p在结肠癌组织中的...[目的]探讨miR-330-5p/PTBP1/CTTN轴调控结肠癌细胞凋亡的潜在机制。[方法]纳入接受根治性结肠切除术的结肠癌患者113例,分析miR-330-5p在结肠癌组织和癌旁组织中的表达水平以及其对总生存率的影响。[结果]miR-330-5p在结肠癌组织中的表达水平较低(0.48±0.22 vs 0.16±0.09,P<0.05)。miR-330-5p高表达的结肠癌患者具有更高的总生存率。过表达miR-330-5p及敲低PTBP1,HCT116细胞的凋亡水平上升(13.02±2.11 vs 68.41±11.08, 12.84±2.16 vs 59.12±10.53,P<0.05)。过表达miR-330-5p后,HCT116细胞中PTBP1的mRNA水平和蛋白水平均下降(0.39±0.04 vs 0.05±0.01,P<0.05)。敲低CTTN后,HCTT6细胞的凋亡水平显著上升(11.70±2.05 vs 55.73±10.19,P<0.05)。过表达miR-330-5p或PTBP1敲低后,CTTN isoform a的表达水平下降。[结论]miR-330-5p能够靶向降解PTBP1 mRNA,减少PTBP1的表达水平,促进结肠癌细胞凋亡。miR-330-5p/PTBP1轴能够调控CTTN外显子的选择性剪接,抑制CTTN isoform a的表达水平并促进结肠癌细胞凋亡。展开更多
Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogr...Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.展开更多
Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular process...Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular processes in certain types of cells,including the growth and differentiation of neuronal cells and activation of immune cells.Its function is regulated by various molecules,including micro RNAs(mi RNAs),long non-coding RNAs(lnc RNAs),and RNA-binding proteins.PTBP1 plays roles in various diseases,particularly in some cancers,including colorectal cancer,renal cell cancer,breast cancer,and glioma.In cancers,it acts mainly as a regulator of glycolysis,apoptosis,proliferation,tumorigenesis,invasion,and migration.The role of PTBP1 in cancer has become a popular research topic in recent years,and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer.In this review,we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.展开更多
胆管癌是一种起病隐匿、侵袭性强、致死率高的原发性恶性肿瘤。多聚嘧啶区结合蛋白1(polypyrimidine tract-binding protein 1,PTBP1)已被报道,在多种类型肿瘤组织中异常高表达并参与癌症进展,但其在胆管癌中的作用仍未见报道。该研究...胆管癌是一种起病隐匿、侵袭性强、致死率高的原发性恶性肿瘤。多聚嘧啶区结合蛋白1(polypyrimidine tract-binding protein 1,PTBP1)已被报道,在多种类型肿瘤组织中异常高表达并参与癌症进展,但其在胆管癌中的作用仍未见报道。该研究旨在探讨PTBP1在胆管癌中的生物学功能,并初步解析其分子机制。本文利用公开的癌症基因组图谱(the cancer genome atlas,TCGA)数据,分析了胆管癌及癌旁组织中的PTBP1 mRNA表达水平。结果显示,PTBP1在胆管癌组织中的表达水平显著高于癌旁组织(P<0.05)。随后,在胆管癌细胞系RBE和HuH28中,通过CCK-8和细胞平板克隆实验,评价了PTBP1对胆管癌细胞生长能力的影响。结果显示,过表达PTBP1可显著促进胆管癌细胞的生长(P<0.01),而敲低PTBP1显著抑制胆管癌细胞的生长(P<0.001)。Transwell和Invasion实验结果显示,过表达PTBP1可显著促进胆管癌细胞的迁移和侵袭(P<0.001),而敲低PTBP1显著抑制胆管癌细胞的迁移和侵袭(P<0.001)。转录物组测序和通路富集分析结果显示,在胆管癌细胞中,敲低PTBP1后上调表达的基因显著富集于p53信号通路;而下调表达的基因显著富集于胆固醇代谢、Rho GTPase和TGF-β等信号通路。基于上述转录物组测序数据,本文还分析发现,敲低PTBP1可导致一系列基因发生异常的mRNA可变剪接事件,例如参与TGF-β调控的TGIF1及与p53活性相关的GNAS基因等。综上所述,PTBP1可能通过调控一系列基因的可变剪接而影响多个癌症相关的信号通路,从而促进胆管癌的进展。展开更多
多聚嘧啶区结合蛋白1(polyrimidine tract binding protein 1,PTBP1)是一种选择性剪接蛋白,通过对Pre-mRNA的选择性剪接以产生多样化的mRNA,从而参与多基因表达的转录调控过程,在肿瘤细胞存活、增殖、转移等过程中发挥重要作用。在不同...多聚嘧啶区结合蛋白1(polyrimidine tract binding protein 1,PTBP1)是一种选择性剪接蛋白,通过对Pre-mRNA的选择性剪接以产生多样化的mRNA,从而参与多基因表达的转录调控过程,在肿瘤细胞存活、增殖、转移等过程中发挥重要作用。在不同肿瘤中,PTBP1的表达水平及生物学功能不同,机制之一可能在于其结合的相互作用蛋白不同。另外,PTBP1与神经系统退行性病变、高血压的发病有关,还参与机体免疫及细胞衰老。本文就PTBP1的结构、功能及其与疾病的相关性等方面作一综述。展开更多
文摘[目的]探讨miR-330-5p/PTBP1/CTTN轴调控结肠癌细胞凋亡的潜在机制。[方法]纳入接受根治性结肠切除术的结肠癌患者113例,分析miR-330-5p在结肠癌组织和癌旁组织中的表达水平以及其对总生存率的影响。[结果]miR-330-5p在结肠癌组织中的表达水平较低(0.48±0.22 vs 0.16±0.09,P<0.05)。miR-330-5p高表达的结肠癌患者具有更高的总生存率。过表达miR-330-5p及敲低PTBP1,HCT116细胞的凋亡水平上升(13.02±2.11 vs 68.41±11.08, 12.84±2.16 vs 59.12±10.53,P<0.05)。过表达miR-330-5p后,HCT116细胞中PTBP1的mRNA水平和蛋白水平均下降(0.39±0.04 vs 0.05±0.01,P<0.05)。敲低CTTN后,HCTT6细胞的凋亡水平显著上升(11.70±2.05 vs 55.73±10.19,P<0.05)。过表达miR-330-5p或PTBP1敲低后,CTTN isoform a的表达水平下降。[结论]miR-330-5p能够靶向降解PTBP1 mRNA,减少PTBP1的表达水平,促进结肠癌细胞凋亡。miR-330-5p/PTBP1轴能够调控CTTN外显子的选择性剪接,抑制CTTN isoform a的表达水平并促进结肠癌细胞凋亡。
基金supported by the National Natural Science Foundation of China,No.82073783(to YY)the Natural Science Foundation of Beijing,No.7212160(to YY).
文摘Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.
基金Project supported by the National Natural Science Foundation of China(Nos.81773179,81272972,and 81472355)the Program for New Century Excellent Talents in University(No.NCET-10-0790)+2 种基金the Hunan Provincial Science and Technology Department(Nos.2016JC 2049 and 2014FJ6006)the Hunan Provincial Natural Science Foundation of China(No.2016JJ2172)the Undergraduate Training Programs for Innovation and Entrepreneurship(Nos.201810533368,GS201910533474,and GS201910533236),China.
文摘Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular processes in certain types of cells,including the growth and differentiation of neuronal cells and activation of immune cells.Its function is regulated by various molecules,including micro RNAs(mi RNAs),long non-coding RNAs(lnc RNAs),and RNA-binding proteins.PTBP1 plays roles in various diseases,particularly in some cancers,including colorectal cancer,renal cell cancer,breast cancer,and glioma.In cancers,it acts mainly as a regulator of glycolysis,apoptosis,proliferation,tumorigenesis,invasion,and migration.The role of PTBP1 in cancer has become a popular research topic in recent years,and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer.In this review,we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
文摘胆管癌是一种起病隐匿、侵袭性强、致死率高的原发性恶性肿瘤。多聚嘧啶区结合蛋白1(polypyrimidine tract-binding protein 1,PTBP1)已被报道,在多种类型肿瘤组织中异常高表达并参与癌症进展,但其在胆管癌中的作用仍未见报道。该研究旨在探讨PTBP1在胆管癌中的生物学功能,并初步解析其分子机制。本文利用公开的癌症基因组图谱(the cancer genome atlas,TCGA)数据,分析了胆管癌及癌旁组织中的PTBP1 mRNA表达水平。结果显示,PTBP1在胆管癌组织中的表达水平显著高于癌旁组织(P<0.05)。随后,在胆管癌细胞系RBE和HuH28中,通过CCK-8和细胞平板克隆实验,评价了PTBP1对胆管癌细胞生长能力的影响。结果显示,过表达PTBP1可显著促进胆管癌细胞的生长(P<0.01),而敲低PTBP1显著抑制胆管癌细胞的生长(P<0.001)。Transwell和Invasion实验结果显示,过表达PTBP1可显著促进胆管癌细胞的迁移和侵袭(P<0.001),而敲低PTBP1显著抑制胆管癌细胞的迁移和侵袭(P<0.001)。转录物组测序和通路富集分析结果显示,在胆管癌细胞中,敲低PTBP1后上调表达的基因显著富集于p53信号通路;而下调表达的基因显著富集于胆固醇代谢、Rho GTPase和TGF-β等信号通路。基于上述转录物组测序数据,本文还分析发现,敲低PTBP1可导致一系列基因发生异常的mRNA可变剪接事件,例如参与TGF-β调控的TGIF1及与p53活性相关的GNAS基因等。综上所述,PTBP1可能通过调控一系列基因的可变剪接而影响多个癌症相关的信号通路,从而促进胆管癌的进展。
文摘多聚嘧啶区结合蛋白1(polyrimidine tract binding protein 1,PTBP1)是一种选择性剪接蛋白,通过对Pre-mRNA的选择性剪接以产生多样化的mRNA,从而参与多基因表达的转录调控过程,在肿瘤细胞存活、增殖、转移等过程中发挥重要作用。在不同肿瘤中,PTBP1的表达水平及生物学功能不同,机制之一可能在于其结合的相互作用蛋白不同。另外,PTBP1与神经系统退行性病变、高血压的发病有关,还参与机体免疫及细胞衰老。本文就PTBP1的结构、功能及其与疾病的相关性等方面作一综述。
