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乙酰转移酶10通过介导盘状蛋白结构域受体1 mRNA的ac4C乙酰化修饰促进宫颈癌细胞的恶性行为 被引量:3
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作者 张雪 汤华 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2022年第5期603-613,共11页
乙酰转移酶10(N-acetyltransferase 10,NAT10)是mRNA乙酰化修饰的关键酶,通过介导ac4C乙酰化修饰(N4-acetylcytidine,ac4C)调控靶基因的表达并调控多种癌症的生物学功能,但NAT10对宫颈癌(cervical cancer,CC)细胞的调控却少有报道。本... 乙酰转移酶10(N-acetyltransferase 10,NAT10)是mRNA乙酰化修饰的关键酶,通过介导ac4C乙酰化修饰(N4-acetylcytidine,ac4C)调控靶基因的表达并调控多种癌症的生物学功能,但NAT10对宫颈癌(cervical cancer,CC)细胞的调控却少有报道。本研究拟探讨NAT10对宫颈癌细胞恶性行为的影响。首先,通过数据库分析发现NAT10高表达与宫颈癌病人预后不良相关。MTT实验和集落形成结果显示,过表达NAT10增加了宫颈癌细胞的生长活性(P<0.05)和增殖能力(P<0.001);Transwell迁移和侵袭结果表明,过表达NAT10提高了宫颈癌细胞的迁移(P<0.01)和侵袭(P<0.05)能力;Western免疫印迹结果显示,过表达NAT10使间皮细胞标志物波形蛋白(vimentin)上调,使上皮细胞标志物E-钙黏着蛋白(E-cadherin)下降。并且,生物信息学分析显示,盘状蛋白结构域受体1(discoidin domain receptor 1,DDR1)可能是NAT10的下游靶基因,RNA结合蛋白免疫沉淀结果表明,NAT10可以直接结合DDR1的mRNA(P<0.05),Western免疫印迹和RT-qPCR的结果表明,过表达NAT10使DDR1蛋白质水平和mRNA水平明显上调(P<0.05)。此外,RNA乙酰化免疫沉淀结果表明,过表达NAT10增加了DDR1 mRNA的乙酰化水平(P<0.001),并且EGFP报告系统进一步确定了NAT10识别DDR1 mRNA的乙酰化位点。mRNA半衰期的结果显示,NAT10可提高DDR1 mRNA的稳定性(P<0.05)。综上所述,NAT10促进宫颈癌细胞的生长、增殖活性以及迁移侵袭能力,其机制是通过对DDR1 mRNA进行乙酰化修饰延长其mRNA的稳定性,这可能为mRNA乙酰化修饰对宫颈癌发生发展的分子机制提供新的见解。 展开更多
关键词 乙酰转移酶10 盘状蛋白结构域受体1 ac4c乙酰化修饰 宫颈癌 迁移 侵袭
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Microstructures and mechanical properties of MgAl_2O_4 particle-reinforced AC4C aluminum composites
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作者 Tateoki IIZUKA 欧阳求保 《Transactions of Nonferrous Metals Society of China》 SCIE EI CAS CSCD 2014年第7期2337-2345,共9页
MgAl2O4 particle-reinforced AC4C based alloy composites were fabricated by the stirring-casting method. The effects of the average sizes and the size distributions of MgAl2O4 particles on the dispersibility were inves... MgAl2O4 particle-reinforced AC4C based alloy composites were fabricated by the stirring-casting method. The effects of the average sizes and the size distributions of MgAl2O4 particles on the dispersibility were investigated, and the microstructures, strength, and fatigue properties of MgAl2O4 particle-reinforced AC4C based alloy composites were evaluated. Tensile strength in the MgAl2O4 particle-reinforced AC4C based alloy composite was increased by using the classified particles. The fatigue limit at 107 cycles in the MgA1204 particle-reinforced AC4C-Cu composite increased by 27% compared to the unreinforced alloy at 250 ~C. Dislocations were observed in the matrix around the MgAl204 particle which resulted from the mismatch of thermal expansion coefficients between MgAl2O4 and Al, and resisted failure and caused fatigue cracks to propagate around the MgAl2O4 particles, resulting in extensive crack deflection and crack bowing which contributed to the improvement of fatigue strength. 展开更多
关键词 MgAl2O4 particle ac4c based aluminum alloy classification of particles composite fatigue tensile strength
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塑性变形后AC4C与Al-17Si合金在半熔融温度下的组织变化
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《特种铸造及有色合金》 CAS CSCD 北大核心 2004年第3期72-72,共1页
关键词 塑性变形 ac4c与Al-17Si合金 组织 半熔融温度 铝合金 轧制
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Fus依赖ac4C修饰调控促进宫颈癌细胞增殖
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作者 金泽源 李咏梅 《天津医科大学学报》 2023年第1期15-20,共6页
目的:探讨Fus RNA结合蛋白(Fus)影响宫颈癌细胞增殖的机制。方法:通过MTT实验观察Fus对宫颈癌细胞HeLa增殖的影响;采用RT-qPCR和Western印迹观察人N-乙酰转移酶10(NAT10)对Fus表达的影响;利用RNA免疫沉淀实验(RIP)检测Fus mRNA的富集情... 目的:探讨Fus RNA结合蛋白(Fus)影响宫颈癌细胞增殖的机制。方法:通过MTT实验观察Fus对宫颈癌细胞HeLa增殖的影响;采用RT-qPCR和Western印迹观察人N-乙酰转移酶10(NAT10)对Fus表达的影响;利用RNA免疫沉淀实验(RIP)检测Fus mRNA的富集情况;通过RNA稳定性实验观察NAT10对Fus mRNA稳定性的影响;基于生物信息学软件PACES预测Fus mRNA上的ac4C修饰位点,构建含有Fus mRNA上ac4C修饰位点的野生型和突变型的EGFP报告质粒,利用EGFP-reporter实验和乙酰化RIP(ac4C-RIP)确定Fus mRNA上发生ac4C修饰位点;最后通过挽救实验观察NAT10介导Fus对宫颈癌细胞增殖的影响。结果:Fus促进宫颈癌HeLa细胞增殖(tFus=14.06,tsh R-Fus=5.74,均P<0.05);Fus蛋白和mRNA的表达水平随NAT10表达增加而增加(tNAT10=10.71,tsh R-NAT10-1=13.17,tsh R-NAT10-2=7.65,均P<0.05);RIP实验结果提示Fus mRNA与NAT10蛋白间存在相互作用(t=4.20,P<0.05),且NAT10过表达细胞中Fus mRNA具有较高ac4C修饰水平(t=30.62,P<0.05);另外,相对于载体对照细胞,NAT10过表达细胞中Fus mRNA的稳定性增高(P<0.01);发现Fus mRNA的925~939序列中的胞嘧啶为ac4C修饰位点;挽救实验结果显示NAT10介导Fus促进宫颈癌细胞的增殖(t=9.67、6.71,P<0.05)。结论:Fus mRNA被NAT10催化发生ac4C修饰,Fus表达水平被上调,继而促进宫颈癌细胞的增殖。 展开更多
关键词 宫颈癌 ac4c FUS NAT10
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NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke
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作者 Li Yang Xiaotong Li +13 位作者 Yaxuan Zhao Hao Chen Can Wang Angrong Wu Xintong Guo Yue Huang Qihui Wang Lingyun Hao Xiaowen Li Ying Ji Jin Ban Guangtian Wang Junli Cao Zhiqiang Pan 《Acta Pharmaceutica Sinica B》 2025年第5期2575-2592,共18页
Although a single nucleotide polymorphism for N-acetyltransferase 10(NAT10)has been identified in patients with early-onset stroke,the role of NAT10 in ischemic injury and the related underlying mechanisms remains elu... Although a single nucleotide polymorphism for N-acetyltransferase 10(NAT10)has been identified in patients with early-onset stroke,the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive.Here,we provide evidence that NAT10,the only known RNA N4-acetylcytidine(ac4C)modification“writer”,is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic(PT)stroke.Pharmacological inhibition of NAT10 with remodelin on Days 3–7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice.Mechanistically,NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1(Timp1)mRNA transcript,which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3(LC3)and progression of astrocyte autophagy.These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke.This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition. 展开更多
关键词 Ischemic stroke ac4c NAT 10 TIMP1 NEUROPROTECTION Functional recovery ASTROCYTE AUTOPHAGY
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mRNA乙酰化修饰在神经系统的功能研究进展 被引量:1
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作者 周海倩 金浩洁银 +2 位作者 张家玮 朱朕 殷东敏 《生理科学进展》 CAS 北大核心 2024年第5期385-392,共8页
RNA存在多种化学修饰,这些修饰赋予核苷酸结构多样性,参与调控RNA代谢、蛋白质合成和多种细胞功能。目前真核细胞中唯一已知的RNA乙酰化修饰即N4-乙酰胞苷(N4-acetylcytidine,ac4C)。以往的研究表明,ac4C主要发生在核糖体RNA(ribosome R... RNA存在多种化学修饰,这些修饰赋予核苷酸结构多样性,参与调控RNA代谢、蛋白质合成和多种细胞功能。目前真核细胞中唯一已知的RNA乙酰化修饰即N4-乙酰胞苷(N4-acetylcytidine,ac4C)。以往的研究表明,ac4C主要发生在核糖体RNA(ribosome RNA,rRNA)和转运RNA(transfer RNA,tRNA)。最近的研究表明,ac4C也可以发生在信使RNA(messenger RNA,mRNA),并促进mRNA的稳定性和翻译效率。相对于被广泛研究的mRNA甲基化修饰(如m6A),人们对ac4C修饰的功能和调控机制的研究尚处于起步阶段。本文主要综述mRNA的ac4C修饰在神经系统生理和病理过程,如学习记忆、疼痛及阿尔茨海默病中的作用,并讨论ac4C研究领域有待解决的关键科学问题,以促进RNA化学修饰调控神经功能的研究。 展开更多
关键词 RNA乙酰化 N4-乙酰胞苷 学习记忆 疼痛 阿尔茨海默病
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基于数值模拟的低压铸造铝合金压气机壳浇注系统的优化 被引量:5
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作者 邢雷杰 范真 +1 位作者 凌智勇 缪友谊 《热加工工艺》 CSCD 北大核心 2016年第3期80-83,共4页
为了消除低压铸造中AC4C铝合金压气机壳铸件的缩松缺陷,利用ProCAST软件进行了铸件充填和凝固过程的数值模拟。根据仿真结果对铸件的浇注系统进行了分析优化。结果表明,浇注时铸件无法按顺序凝固,且缩松较多。将铸件反置,并使充填压力从... 为了消除低压铸造中AC4C铝合金压气机壳铸件的缩松缺陷,利用ProCAST软件进行了铸件充填和凝固过程的数值模拟。根据仿真结果对铸件的浇注系统进行了分析优化。结果表明,浇注时铸件无法按顺序凝固,且缩松较多。将铸件反置,并使充填压力从0.035 MPa减小至0.028 MPa,金属液的充填过程趋于稳定,但铸件热节处仍存在缩松。最后,通过增加铸件冒口,缩松缺陷基本消除。根据仿真结果成功铸造出形状完整、表面光滑和显微结构致密的AC4C铝合金压气机壳铸件。 展开更多
关键词 低压铸造 ac4c铝合金 数值模拟 缺陷
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Thermal deformation of aluminum alloy casting materials for tire mold by numerical analysis 被引量:7
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作者 Hee-Sung YOON Je-Se CHOI Yool-Kwon OH 《中国有色金属学会会刊:英文版》 CSCD 2012年第S3期859-863,共5页
Thermal deformation of aluminum alloy casting materials for manufacturing the tire mold was numerically investigated.The AC7A and AC4C casting material was selected as casting material and the metal casting device was... Thermal deformation of aluminum alloy casting materials for manufacturing the tire mold was numerically investigated.The AC7A and AC4C casting material was selected as casting material and the metal casting device was used in order to manufacture the mold product of automobile tire in the actual industrial field.The temperature distribution and the cooling time of casting materials were numerically calculated by finite element analysis (FEA).Also,the thermal deformation such as displacement and stress distribution was calculated from the temperature results.The thermal deformation was closely related to the temperature difference between the surface and inside of the casting.The numerical analysis results reveal that the thermal deformation of AC7A casting material is higher than that of AC4C casting material.Also,the thermal deformation results at the central part are larger than that on the side of casting because of the shrinkage caused by the cooling speed difference. 展开更多
关键词 thermal DEFORMATION FINITE ELEMENT analysis AC7A CASTING MATERIAL ac4c CASTING MATERIAL
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RNA修饰在胃癌发生发展中的作用机制研究进展
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作者 徐佳雯 王强 王守宇 《肿瘤防治研究》 CAS 2023年第8期738-744,共7页
胃癌的发生与环境、遗传和表观遗传因素密切相关。目前,RNA修饰是表观遗传领域的研究前沿和热点。随着分析化学和高通量测序技术的进步,解析RNA修饰的新技术和新方法不断涌现。大量研究已经证实RNA修饰参与多种疾病的发生和发展。最近... 胃癌的发生与环境、遗传和表观遗传因素密切相关。目前,RNA修饰是表观遗传领域的研究前沿和热点。随着分析化学和高通量测序技术的进步,解析RNA修饰的新技术和新方法不断涌现。大量研究已经证实RNA修饰参与多种疾病的发生和发展。最近研究发现m6A、m5C、ac4C等RNA修饰调控胃癌、肝癌、结直肠癌、白血病等多种肿瘤的恶性进程。本文就RNA修饰在胃癌发生发展中的研究现状和作用机制作系统综述,并讨论其在胃癌诊断和治疗方面的潜在价值。 展开更多
关键词 RNA修饰 胃癌 m6A m5C ac4c
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C_3N_4/AC结构对二氯乙烷催化热裂解性能的影响 被引量:1
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作者 刘政 孙玺 +2 位作者 张健 秦玉才 宋丽娟 《石油化工高等学校学报》 CAS 2018年第6期17-23,共7页
采用等摩尔浸渍法,利用含相同物质的量氮的氰胺、硫脲、尿素作为前驱体,以活性炭为载体制备C_3N_4/AC催化剂。运用固定床反应器评价了C_3N_4/AC催化剂对1,2-二氯乙烷催化热裂解的反应性能,并采用SEM、XRD、BET、XPS、TGA表征了催化剂形... 采用等摩尔浸渍法,利用含相同物质的量氮的氰胺、硫脲、尿素作为前驱体,以活性炭为载体制备C_3N_4/AC催化剂。运用固定床反应器评价了C_3N_4/AC催化剂对1,2-二氯乙烷催化热裂解的反应性能,并采用SEM、XRD、BET、XPS、TGA表征了催化剂形貌、结构及表面组成等性质。结果表明,0.110 mol前驱体制备的催化剂初始活性和选择性都接近100%,但催化剂稳定性差异明显,以尿素为前躯体制备的C_3N_4/AC催化剂稳定性最高。然而,通过降低前驱体负载量合成的C_3N_4/AC催化剂结构与形貌及催化裂解性能均有差异。当负载量降到每10 g活性炭负载0.057 mol的氮时,以尿素为前躯体制备的C_3N_4/AC催化剂对1,2-二氯乙烷裂解催化活性较好、稳定性最高。不同前驱体合成的氮化碳形貌不同,硫脲、氰胺虽然可获得更多的氮化碳,但是所形成的氮化碳容易团聚从而影响了催化活性,尿素是用于该催化剂合成最优的前驱体。 展开更多
关键词 前躯体 C3N4/AC 1 2-二氯乙烷 催化热裂解
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一种基于语义特征预测N4-乙酰胞苷修饰位点的方法
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作者 郑杨 《邵阳学院学报(自然科学版)》 2021年第6期78-87,共10页
目的N4-乙酰胞苷(ac4C)作为真核mRNA中唯一的乙酰化修饰,可以影响mRNA解码效率,有助于在翻译过程中正确读取密码子,并提高翻译效率和mRNA的稳定性。ac4C已经被证实与多种人类疾病相关,尤其是和癌症也有相关性,但准确判别ac4C修饰得位点... 目的N4-乙酰胞苷(ac4C)作为真核mRNA中唯一的乙酰化修饰,可以影响mRNA解码效率,有助于在翻译过程中正确读取密码子,并提高翻译效率和mRNA的稳定性。ac4C已经被证实与多种人类疾病相关,尤其是和癌症也有相关性,但准确判别ac4C修饰得位点仍然有较大困难,所以,提出了一种基于深度学习的方法用于识别ac4C位点的模型。方法用长短时记忆网络和卷积神经网络搭建深度学习模型提取序列中的语义特征,以随机森林作为最终分类器。结果所提出的方法在5倍交叉验证中AUC达0.8796,在独立测试中AUC达0.8718,均达到一个较好的结果。在5倍交叉验证中灵敏度达0.6491,在独立测试中灵敏度达0.6567,超过了最先进方法的灵敏度。结论与使用的传统特征进行了对比,语义特征具有更好的性能,有助于更准确识别ac4C的修饰位点。 展开更多
关键词 N4-乙酰胞苷 深度学习 语义特征 随机森林
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N-acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4-acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA 被引量:23
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作者 Xiao Zheng Qi Wang +6 位作者 You Zhou Dachuan Zhang Yiting Geng Wenwei Hu Changping Wu Yufang Shi Jingting Jiang 《Cancer Communications》 SCIE 2022年第12期1347-1366,共20页
Background:N-acetyltransferase 10(NAT10)is the only enzyme known tomediate the N4-acetylcytidine(ac4C)modification of mRNA and is crucial formRNA stability and translation efficiency.However,its role in cancer develop... Background:N-acetyltransferase 10(NAT10)is the only enzyme known tomediate the N4-acetylcytidine(ac4C)modification of mRNA and is crucial formRNA stability and translation efficiency.However,its role in cancer development and prognosis has not yet been explored.This study aimed to examine the possible role of NAT10 in colon cancer.Methods:The expression levels ofNAT10were evaluated by immunohistochemical analyses with a colon cancer tissue microarray,and its prognostic value in patients was further analyzed.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were performed to analyze NAT10 expression in harvested colon cancer tissues and cell lines.Stable NAT10-knockdown and NAT10-overexpressing colon cancer cell lines were constructed using lentivirus.The biological functions of NAT10 in colon cancer cell lines were analyzed in vitro by Cell Counting Kit-8(CCK-8),wound healing,Transwell,cell cycle,and ferroptosis assays.Xenograft models were used to analyze the effect of NAT10 on the tumorigenesis and metastasis of colon cancer cells in vivo.Dot blotting,acetylated RNA immunoprecipitation-qPCR,and RNA stability analyses were performed to explore the mechanism by which NAT10 functions in colon cancer progression.Results:NAT10 was upregulated in colon cancer tissues and various colon cancer cell lines.This increased NAT10 expression was associated with shorter patient survival.Knockdown of NAT10 in two colon cancer cell lines(HT-29 and LoVo)impaired the proliferation,migration,invasion,tumor formation and metastasis of these cells,whereas overexpression of NAT10 promoted these abilities.Further analysis revealed that NAT10 exerted a strong effect on the mRNA stability and expression of ferroptosis suppressor protein 1(FSP1)in HT-29 and LoVo cells.In these cells,FSP1 mRNA was found to be modified by ac4C acetylation,and this epigenetic modification was associated with the inhibition of ferroptosis.Conclusions:Our study revealed that NAT10 plays a critical role in colon cancer development by affecting FSP1 mRNA stability and ferroptosis,suggesting that NAT10 could be a novel prognostic and therapeutic target in colon cancer. 展开更多
关键词 Colon cancer N-acetyltransferase 10(NAT10) N4-acetylcytidine(ac4c) Ferroptosis suppressor protein 1(FSP1) Ferroptosis mRNA stability RNA acetylation
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The Ever-Expanding Role of C4/AC4 in Geminivirus Infection: Punching above Its Weight? 被引量:2
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作者 Vincent N. Fondong 《Molecular Plant》 SCIE CAS CSCD 2019年第2期145-147,共3页
Geminiviruses (family Geminiviridae) are among the most devastating plant pathogens worldwide, causing heavy losses on food and cash crops and representing a threat to global food security and sustainability. These vi... Geminiviruses (family Geminiviridae) are among the most devastating plant pathogens worldwide, causing heavy losses on food and cash crops and representing a threat to global food security and sustainability. These viruses have very compact genomes comprising one (monopartite) or two (bipartite) circular singlestranded DNA (ssDNA) molecules, each ranging from 2.6 to 2.8 kb. 展开更多
关键词 C4/AC4 GEMINIVIRUS Infection DNA
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