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MORC4在结直肠癌中的表达及其对结直肠癌细胞生物学行为的影响
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作者 林潇 陈灵斌 +3 位作者 刘炳辉 陈慧 黄合 游淑清 《浙江医学》 CAS 2023年第19期2041-2046,I0004,共7页
目的探讨染色质重塑蛋白家族CW型锌指结构蛋白4(MORC4)在结直肠癌(CRC)中的表达及其对CRC细胞生物学行为的影响。方法收集2018年1月至2019年2月台州市第一人民医院经手术切除的CRC组织及癌旁组织,选择CRC细胞系(HCT-15、SW480、SW620、D... 目的探讨染色质重塑蛋白家族CW型锌指结构蛋白4(MORC4)在结直肠癌(CRC)中的表达及其对CRC细胞生物学行为的影响。方法收集2018年1月至2019年2月台州市第一人民医院经手术切除的CRC组织及癌旁组织,选择CRC细胞系(HCT-15、SW480、SW620、DLD-1、HCT116)和人结肠上皮细胞株(NCM460)。采用q RT-PCR方法检测80例CRC组织及其相应的癌旁组织中MORC4 mRNA的表达。采用免疫组化法检测150例CRC组织及60例癌旁组织中MORC4蛋白表达情况,分析MORC4蛋白高表达与患者临床病理特征的关系。绘制Kaplan-Meier生存曲线分析MORC4蛋白表达与CRC患者预后关系。选择MORC4 mRNA表达水平较高的DLD-1细胞为研究对象,构建MORC4敲低细胞DLD-1(敲低组)及空白对照组、阴性对照组,采用细胞增殖/凋亡检测(CCK-8)法、划痕实验及Transwell细胞侵袭实验检测CRC细胞的增殖、迁移及侵袭情况。结果相比癌旁组织,CRC组织中MORC4 mRNA表达水平及MORC蛋白表达率均显著升高(均P<0.05)。不同性别、年龄、肿瘤位置(左右侧)、肿瘤直径、T分期的患者CRC组织MORC4蛋白高表达率比较,差异均无统计学意义(均P>0.05);不同分化程度、淋巴结转移情况、远处转移情况、肿瘤-淋巴结-转移分期及血清癌胚抗原水平的患者CRC组织MORC4高表达率比较,差异均有统计学意义(均P<0.05)。与MORC4低表达患者相比,MORC4高表达患者预后更差(P<0.01)。相比空白对照组和阴性对照组,敲低组细胞24、48、72 h增殖能力均显著降低,迁移能力显著降低,穿基底膜细胞数量明显减少(均P<0.05)。结论CRC患者MORC4表达上调与不良预后相关,MORC4可能是CRC的一个预后标志物,敲低MORC4可抑制CRC细胞增殖、迁移和侵袭。 展开更多
关键词 染色质重塑蛋白家族CW型锌指结构蛋白4 结直肠癌 免疫组化 生物学行为
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表观遗传学改变与中药活性成分靶向抗肿瘤的研究进展 被引量:2
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作者 黄力 严小蓉 +2 位作者 吴君华 冯岗 徐维国 《实用临床医药杂志》 CAS 2022年第15期143-148,共6页
表观遗传学在癌症临床治疗和预防中占据重要地位。表观遗传学改变如DNA甲基化、组蛋白修饰、非编码RNA(ncRNA)、染色质结构重塑等是基于对DNA碱基序列以外的基因调控,不影响DNA的碱基序列。表观遗传改变通过调控抑癌或促癌基因转录或相... 表观遗传学在癌症临床治疗和预防中占据重要地位。表观遗传学改变如DNA甲基化、组蛋白修饰、非编码RNA(ncRNA)、染色质结构重塑等是基于对DNA碱基序列以外的基因调控,不影响DNA的碱基序列。表观遗传改变通过调控抑癌或促癌基因转录或相关基因的表达、沉默或DNA复制和修复或端粒调节、着丝粒稳定性、染色体分离等过程参与临床恶性肿瘤的多种生物学过程,常被应用于早期恶性肿瘤的临床诊断和预后检测。因此,针对表观遗传改变的药物广泛应用于多种恶性肿瘤的临床治疗,但仍存在耐药性、不良反应及应答率低等问题,极大地影响患者生活质量和预后。中医药在恶性肿瘤治疗上疗效显著,多通路、多分子、多靶点的中药活性成分的抗肿瘤作用机制成为研究热点,基于表观遗传学改变的抗肿瘤中药或联合表观遗传改变的药物对恶性肿瘤的治疗具有重要临床价值。本文从表观遗传学改变与相关药物、基于表观遗传学改变抗肿瘤作用、中药活性成分通过调节甲基转移酶(DNMT)、组蛋白修饰、ncRNA、染色质结构重塑和靶向抗肿瘤等方面对中药活性成分的抗肿瘤机制进行综述,以期从表观遗传学改变角度为抗肿瘤中药新药的研究提供思路。 展开更多
关键词 中药 抗肿瘤 DNA甲基化 组蛋白修饰 非编码RNA 染色质结构重塑
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Dynamic regulation of alternative splicing and chromatin structure in Drosophila gonads revealed by RNA-seq 被引量:10
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作者 Qiang Gan Iouri Chepelev +4 位作者 Gang Wei Lama Tarayrah Kairong Cui Keji Zhao Xin Chen 《Cell Research》 SCIE CAS CSCD 2010年第7期763-783,共21页
Both transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding... Both transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding of eukaryotic transcriptomes to a new level, because it can resolve both gene expression level and alternative splicing events simultaneously. To gain a better understanding of cellular differentiation in gonads, we analyzed mRNA profiles from Drosophila testes and ovaries using RNA-seq. We identified a set of genes that have sex-specific isoforms in wild-type (WT) gonads, including several transcription factors. We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors. Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell-enriched bag of marbles (barn) mutant testis, but downregulated upon differentiation in WT testis. Consistent with this, we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level, but not by alternative splicing. Unexpectedly, we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell-enriched bam testis. More interestingly, chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis, suggesting that these cells may possess dynamic chromatin architecture. Finally, our data revealed many new features of the Drosophila gonadal transcriptomes, and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila. Our data provided a foundation for the systematic study of gene expression and alternative splicing in many interesting areas of germ cell biology in Droso- phila, such as the molecular basis for sexual dimorphism and the regulation of the proliferation vs terminal differentiation programs in germline stem cell lineages. The GEO accession number for the raw and analyzed RNA-seq data is GSE16960. 展开更多
关键词 TRANSCRIPTION alternative splicing differentiation TESTIS OVARY DROSOPHILA
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