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
[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
In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively...In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively known as the ribonome, are tightly controlled and carried out by a plethora of trans-acting RNA-binding proteins （RBPs） that bind to specific cis elements throughout the RNA sequence. Within the nervous system, the role of RBPs in brain function turns out to be essential due to the architectural complexity of neurons exemplified by a relatively small somal size and an extensive network of projections and connections, Thus far, RBPs have been shown to be indispensable for several aspects of neurogenesis, neurite outgrowth, synapse formation, and plasticity. Consequently, perturbation of their function is central in the etiology of an ever-growing spectrum of neurological diseases, including fragile X syndrome and the neurodegenerative disorders frontotemporal lobar degeneration and amyotrophic lateral sclerosis.展开更多
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.
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.
基金funded by grants from the Greek General Secretariat for Research and Development,Ministry of Education
文摘In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively known as the ribonome, are tightly controlled and carried out by a plethora of trans-acting RNA-binding proteins （RBPs） that bind to specific cis elements throughout the RNA sequence. Within the nervous system, the role of RBPs in brain function turns out to be essential due to the architectural complexity of neurons exemplified by a relatively small somal size and an extensive network of projections and connections, Thus far, RBPs have been shown to be indispensable for several aspects of neurogenesis, neurite outgrowth, synapse formation, and plasticity. Consequently, perturbation of their function is central in the etiology of an ever-growing spectrum of neurological diseases, including fragile X syndrome and the neurodegenerative disorders frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
