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组蛋白乙酰转移酶MYST2对胰腺癌的影响
编辑人员丨6天前
目的:探讨组蛋白乙酰转移酶MYST2在胰腺癌细胞的蛋白质表达水平及其对诊断胰腺癌的价值。方法:收集2017年12月1日至2020年6月30日于北京协和医院行手术切除并经病理学确诊的54例胰腺癌患者的癌组织和对应癌旁组织(距离手术切缘>5 cm)。对人胰腺癌细胞系ASPC1和BXPC3进行敲低处理(ASPC1敲低组和BXPC3敲低组),对CFPAC1和SW1990进行过表达处理(CFPAC1过表达组和SW1990过表达组),未经处理的为ASPC1、BXPC3、CFPAC1和SW1990空载对照组。采用蛋白质印迹法分别检测不同病理分化程度患者的胰腺癌细胞,人正常胰腺导管上皮细胞系HPDE和人胰腺癌细胞系ASPC1、BXPC3、CFPAC1、SW1990,以及敲低组、过表达组和空载对照组的MYST2蛋白质水平。采用实时无标记动态细胞分析技术,Transwell迁移、侵袭实验和平板集落形成实验比较敲低组、过表达组与空载对照组细胞的增殖活性,迁移、侵袭和集落形成能力。对54例患者的胰腺癌及其癌旁组织进行MYST2免疫组织化学评分,并绘制受试者操作特征曲线分析MYST2不同表达水平对诊断胰腺癌的价值。统计学方法采用独立样本 t检验和方差分析。 结果:54例胰腺癌患者病理切片中,高分化13例,中分化24例,低分化15例,未分化2例,胰腺癌细胞MYST2蛋白质表达水平分别为3.12±1.67、2.87±1.59、2.12±1.03、1.08±0.34,差异有统计学意义( F=1.241, P<0.05)。4种胰腺癌细胞系ASPC1、BXPC3、CFPAC1、SW1990的MYST2表达水平均高于正常胰腺导管上皮细胞系HPDE(1.41±0.47、1.40±0.93、1.13±0.62、1.71±0.46比0.82±0.25),差异均有统计学意义( t=1.625、1.577、1.319、1.832, P均<0.05)。BXPC3敲低组MYST2水平低于BXPC3空载对照组(0.39±0.12比0.75±0.34),ASPC1敲低组低于ASPC1空载对照组(0.43±0.22比0.82±0.48),CFPAC1过表达组高于CFPAC1空载对照组(1.38±0.45比0.82±0.37),SW1990过表达组高于SW1990空载对照组(1.34±0.65比0.51±0.22),差异均有统计学意义( t=1.414、1.378、1.319、1.934, P均<0.05)。ASPC1敲低组细胞增殖较ASPC1空载对照组缓慢,80 h增殖峰值低于空载对照组(1.02±0.77比4.31±2.45);BXPC3敲低组细胞增殖较BXPC3空载对照组缓慢,80 h增殖峰值低于空载对照组(0.91±0.24比2.84±0.53);SW1990过表达组胰腺癌细胞增殖较SW1990空载对照组快,80 h增殖峰值高于空载对照组(3.10±0.67比1.04±0.17);CFPAC1过表达组胰腺癌细胞增殖较CFPAC1空载对照组快,80 h增殖峰值高于空载对照组( 5.45±1.13比1.01±0.29),差异均有统计学意义( t=1.427、1.316、1.292、1.501, P均<0.05)。在迁移能力检测中,ASPC1敲低组穿过Transwell小室的细胞少于ASPC1空载对照组(34.08±17.62比118.76±5.31),BXPC3敲低组少于BXPC3空载对照组(18.62±9.64比57.90±12.67);SW1990过表达组多于SW1990空载对照组(134.84±24.65比37.82±6.73),CFPAC1过表达组多于CFPAC1空载对照组(65.79±27.46比11.68±5.13),差异均有统计学意义( t=1.475、1.322、1.437、1.219, P均<0.05)。在侵袭能力检测中,ASPC1敲低组穿过Transwell小室的细胞少于ASPC1空载对照组(9.79±5.75比45.76±12.71),BXPC3敲低组少于BXPC3空载对照组(23.46±11.13比84.92±17.65),SW1990过表达组多于SW1990空载对照组(156.42±34.50比42.13±22.17),CFPAC1过表达组多于CFPAC1空载对照组(112.64±47.82比39.09±17.23),差异均有统计学意义( t=1.324、1.635、1.423、1.119, P均<0.05)。在集落形成数量方面,ASPC1敲低组少于ASPC1空载对照组(13.15±6.42比86.79±35.17),BXPC3敲低组少于BXPC3空载对照组(14.93±9.30比52.93±15.76);SW1990过表达组多于SW1990空载对照组(129.10±57.31比62.42±37.43),CFPAC1过表达组多于CFPAC1空载对照组(157.98±66.45比74.35±34.69),差异均有统计学意义( t=1.148、1.290、1.274、1.462, P均<0.05)。胰腺癌组织MYST2评分高于癌旁胰腺组织[(3.04±2.23)分比(1.32±0.70)分],差异有统计学意义( t=3.479, P<0.05)。当MYST免疫组织化学总评分为3分时,曲线下面积最大(0.888,95%可信区间0.827~0.948),约登指数为0.56。 结论:MYST2与胰腺癌细胞增殖、侵袭、迁移能力有关,其高表达可促进胰腺癌发展。
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编辑人员丨6天前
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The Arabidopsis NuA4 histone acetyltransferase complex is required for chlorophyll biosynthesis and photosynthesis
编辑人员丨2023/8/5
Although two Enhancer of Polycomb-like proteins, EPL1A and EPL1B (EPL1A/B), are known to be conserved and characteristic subunits of the NuA4-type histone acetyltransferase complex in Arabidopsis thaliana, the biological function of EPL1A/B and the mechanism by which EPL1A/B function in the complex remain unknown. Here, we report that EPL1A/B are required for the histone acetyltransferase activity of the NuA4 complex on the nucleosomal histone H4 in vitro and for the enrichment of histone H4K5 acetylation at thousands of protein-coding genes in vivo. Our results suggest that EPL1A/B are required for linking the NuA4 catalytic subunits HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY 1 (HAM1) and HAM2 with accessory subunits in the NuA4 complex. EPL1A/B function redundantly in regulating plant development especially in chlorophyll biosynthesis and de-etiolation. The EPL1A/B-dependent transcription and H4K5Ac are enriched at genes involved in chlorophyll bio-synthesis and photosynthesis. We also find that EAF6, another characteristic subunit of the NuA4 complex, contributes to de-etiolation. These re-sults suggest that the Arabidopsis NuA4 complex components function as a whole to mediate his-tone acetylation and transcriptional activation specifically at light-responsive genes and are critical for photomorphogenesis.
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编辑人员丨2023/8/5
