克鲁佩尔相关盒锌指蛋白(KRAB-ZFPs, Krüppel-Associated Box Zinc Finger Proteins)是人类基因组中数量最多的转录因子家族,广泛参与基因表达调控、生长发育及细胞信号通路的调节。锌指蛋白433 (ZNF433, Zinc Finger Protein 433...克鲁佩尔相关盒锌指蛋白(KRAB-ZFPs, Krüppel-Associated Box Zinc Finger Proteins)是人类基因组中数量最多的转录因子家族,广泛参与基因表达调控、生长发育及细胞信号通路的调节。锌指蛋白433 (ZNF433, Zinc Finger Protein 433)基因是KRAB-ZFPs家族的成员,其分子功能和在癌症中的作用尚未被充分研究。在前列腺癌中,ZNF433高表达可促进β-catenin/TCF复合物的形成,激活Wnt/β-catenin信号通路,进而促进癌细胞增殖和迁移,表现为促癌因子。而在肾透明细胞癌中,ZNF433表达下调,其低表达与更高级别的肿瘤分期及较差预后相关,可能与启动子区域的高甲基化导致的转录沉默有关,从而影响肿瘤的发生与进展,表现为抑癌因子。此外,ZNF433的异常表达与癌症患者的临床预后密切相关,提示其在癌症诊断和治疗中的潜在应用价值。本文综述了ZNF433的分子结构、生物学功能及其在前列腺癌和肾透明细胞癌中的作用机制,并探讨了其作为癌症生物标志物和治疗靶点的潜力。未来,进一步解析ZNF433的直接靶基因、上游调控机制及其与肿瘤微环境的相互作用,将有助于深入理解其在癌症中的功能,并为精准治疗提供新的策略。Krüppel-Associated Box Zinc Finger Proteins (KRAB-ZFPs) are the largest family of transcription factors in the human genome, extensively involved in gene expression regulation, development, and modulation of cellular signaling pathways. Zinc Finger Protein 433 (ZNF433) is a member of the KRAB-ZFPs family, but its molecular function and role in cancer have not been fully elucidated. In prostate cancer, ZNF433 overexpression promotes the formation of the β-catenin/TCF complex, activating the Wnt/β-catenin signaling pathway, which subsequently enhances cancer cell proliferation and migration, functioning as an oncogene. In contrast, in clear cell renal cell carcinoma, ZNF433 expression is downregulated, and its low expression is associated with higher tumor grade, advanced stage, and poorer prognosis. This downregulation may be linked to promoter hypermethylation, leading to transcriptional silencing, thereby influencing tumorigenesis and progression, functioning as a tumor suppressor. Moreover, abnormal expression of ZNF433 is closely correlated with clinical prognosis in cancer patients, suggesting its potential application in cancer diagnosis and therapy. This review summarizes the molecular structure, biological functions, and roles of ZNF433 in prostate cancer and ccRCC, while also exploring its potential as a biomarker and therapeutic target for cancer. In the future, further elucidation of ZNF433’s direct target genes, upstream regulatory mechanisms, and interactions with the tumor microenvironment will help deepen our understanding of its role in cancer and provide new strategies for precision therapy.展开更多
目的对D19S433基因座稀有等位基因8.2,用分子生物学方法,验证其命名,对突变发生的位置进行确认和分析。方法设计引物对目的基因进行扩增和测序,验证常规命名法。将测序所得序列与D19S433基因座的基础序列进行比对分析。结果Goldeneye DN...目的对D19S433基因座稀有等位基因8.2,用分子生物学方法,验证其命名,对突变发生的位置进行确认和分析。方法设计引物对目的基因进行扩增和测序,验证常规命名法。将测序所得序列与D19S433基因座的基础序列进行比对分析。结果Goldeneye DNA 20A和AGCU EX22亲子鉴定系统联合检测,相互比对,确定在检案中发现的分型标准物之外(Off⁃ladder,OL)的等位基因为D19S433基因座的稀有等位基因。经常规漂移校正计算该等位基因为8.2。测序后分析其重复序列确定该等位基因为8.2无误。结论对STR分型中发现的稀有等位基因进行测序,分析其重复序列,可以准确的对其进行命名,确定稀有等位基因突变的位置,丰富中国人群STR数据信息。展开更多
目的研究肝细胞肝癌(HCC)中长链非编码RNA(LncRNA)氧化应激反应丝氨酸丰富1反义RNA1(OSER1-AS1)靶向调控微小RNA(miR)-433-3p的作用及生物学意义。方法选择唐山市第九医院手术切除的HCC组织和癌旁组织,培养HCC细胞株SMMC-7721、HepG2、M...目的研究肝细胞肝癌(HCC)中长链非编码RNA(LncRNA)氧化应激反应丝氨酸丰富1反义RNA1(OSER1-AS1)靶向调控微小RNA(miR)-433-3p的作用及生物学意义。方法选择唐山市第九医院手术切除的HCC组织和癌旁组织,培养HCC细胞株SMMC-7721、HepG2、MHCC97H及正常肝细胞株HL-7702。检测LncRNA OSER1-AS1、miR-433-3p的表达水平,比较HCC组织与癌旁组织、HCC细胞株与正常肝细胞株中LncRNA OSER1-AS1、miR-433-3p表达水平的差异。对转染MHCC97H细胞进行分组,转染阴性对照(NC)-siRNA为si-NC组,转染LncRNA OSER1-AS1-siRNA为si-OSER1-AS1组,转染LncRNA OSER1-AS1-siRNA及NC miR为si-OSER1-AS1+miR-NC组,转染LncRNA OSER1-AS1-siRNA及miR-433-3p抑制物为si-OSER1-AS1+miR-433-3p抑制物组。检测细胞增殖活力、凋亡率、增殖细胞核抗原(PCNA)及裂解型caspase-3(cleaved caspase-3)的表达水平,采用双荧光素酶报告基因实验验证LncRNA OSER1-AS1靶向miR-433-3p。结果HCC组织中LncRNA OSER1-AS1的表达水平高于癌旁组织(1.77±0.34 vs1.00±0.21)、miR-433-3p的表达水平低于癌旁组织(0.65±0.09 vs 1.00±0.28)(P<0.05)且LncRNA OSER1-AS1与miR-433-3p呈负相关(r=-0.351,P<0.05);HCC细胞株中LncRNA OSER1-AS1的表达水平高于HL-7702细胞、miR-433-3p的表达水平低于HL-7702细胞(P<0.05)且MHCC97H细胞中上述变化最显著。si-OSER1-AS1组MHCC97H细胞中LncRNA OSER1-AS1、PCNA的表达水平及增殖活力低于si-NC组(0.37±0.05 vs 1.00±0.11,0.33±0.05 vs 0.92±0.12,0.51±0.09 vs 1.03±0.12),miR-433-3p、cleaved caspase-3的表达水平及凋亡率高于si-NC组(1.88±0.25 vs 1.00±0.09,0.96±0.11 vs 0.44±0.06,9.39%±1.15%vs 3.82%±0.55%)(P<0.05);si-OSER1-AS1+miR-433-3p抑制物组MHCC97H细胞中cleaved caspase-3表达水平及凋亡率低于si-OSER1-AS1+miR-NC组(0.27±0.05 vs 0.91±0.10,6.04%±0.77%vs 11.32%±1.32%),PCNA的表达水平及增殖活力高于si-OSER1-AS1+miR-NC组(0.94±0.12 vs 0.48±0.06,0.95±0.11 vs 0.34±0.05)(P<0.05)。结论LncRNA OSER1-AS1靶向miR-433-3p调控HCC细胞的增殖和凋亡。展开更多
文摘克鲁佩尔相关盒锌指蛋白(KRAB-ZFPs, Krüppel-Associated Box Zinc Finger Proteins)是人类基因组中数量最多的转录因子家族,广泛参与基因表达调控、生长发育及细胞信号通路的调节。锌指蛋白433 (ZNF433, Zinc Finger Protein 433)基因是KRAB-ZFPs家族的成员,其分子功能和在癌症中的作用尚未被充分研究。在前列腺癌中,ZNF433高表达可促进β-catenin/TCF复合物的形成,激活Wnt/β-catenin信号通路,进而促进癌细胞增殖和迁移,表现为促癌因子。而在肾透明细胞癌中,ZNF433表达下调,其低表达与更高级别的肿瘤分期及较差预后相关,可能与启动子区域的高甲基化导致的转录沉默有关,从而影响肿瘤的发生与进展,表现为抑癌因子。此外,ZNF433的异常表达与癌症患者的临床预后密切相关,提示其在癌症诊断和治疗中的潜在应用价值。本文综述了ZNF433的分子结构、生物学功能及其在前列腺癌和肾透明细胞癌中的作用机制,并探讨了其作为癌症生物标志物和治疗靶点的潜力。未来,进一步解析ZNF433的直接靶基因、上游调控机制及其与肿瘤微环境的相互作用,将有助于深入理解其在癌症中的功能,并为精准治疗提供新的策略。Krüppel-Associated Box Zinc Finger Proteins (KRAB-ZFPs) are the largest family of transcription factors in the human genome, extensively involved in gene expression regulation, development, and modulation of cellular signaling pathways. Zinc Finger Protein 433 (ZNF433) is a member of the KRAB-ZFPs family, but its molecular function and role in cancer have not been fully elucidated. In prostate cancer, ZNF433 overexpression promotes the formation of the β-catenin/TCF complex, activating the Wnt/β-catenin signaling pathway, which subsequently enhances cancer cell proliferation and migration, functioning as an oncogene. In contrast, in clear cell renal cell carcinoma, ZNF433 expression is downregulated, and its low expression is associated with higher tumor grade, advanced stage, and poorer prognosis. This downregulation may be linked to promoter hypermethylation, leading to transcriptional silencing, thereby influencing tumorigenesis and progression, functioning as a tumor suppressor. Moreover, abnormal expression of ZNF433 is closely correlated with clinical prognosis in cancer patients, suggesting its potential application in cancer diagnosis and therapy. This review summarizes the molecular structure, biological functions, and roles of ZNF433 in prostate cancer and ccRCC, while also exploring its potential as a biomarker and therapeutic target for cancer. In the future, further elucidation of ZNF433’s direct target genes, upstream regulatory mechanisms, and interactions with the tumor microenvironment will help deepen our understanding of its role in cancer and provide new strategies for precision therapy.
文摘目的对D19S433基因座稀有等位基因8.2,用分子生物学方法,验证其命名,对突变发生的位置进行确认和分析。方法设计引物对目的基因进行扩增和测序,验证常规命名法。将测序所得序列与D19S433基因座的基础序列进行比对分析。结果Goldeneye DNA 20A和AGCU EX22亲子鉴定系统联合检测,相互比对,确定在检案中发现的分型标准物之外(Off⁃ladder,OL)的等位基因为D19S433基因座的稀有等位基因。经常规漂移校正计算该等位基因为8.2。测序后分析其重复序列确定该等位基因为8.2无误。结论对STR分型中发现的稀有等位基因进行测序,分析其重复序列,可以准确的对其进行命名,确定稀有等位基因突变的位置,丰富中国人群STR数据信息。
文摘目的研究肝细胞肝癌(HCC)中长链非编码RNA(LncRNA)氧化应激反应丝氨酸丰富1反义RNA1(OSER1-AS1)靶向调控微小RNA(miR)-433-3p的作用及生物学意义。方法选择唐山市第九医院手术切除的HCC组织和癌旁组织,培养HCC细胞株SMMC-7721、HepG2、MHCC97H及正常肝细胞株HL-7702。检测LncRNA OSER1-AS1、miR-433-3p的表达水平,比较HCC组织与癌旁组织、HCC细胞株与正常肝细胞株中LncRNA OSER1-AS1、miR-433-3p表达水平的差异。对转染MHCC97H细胞进行分组,转染阴性对照(NC)-siRNA为si-NC组,转染LncRNA OSER1-AS1-siRNA为si-OSER1-AS1组,转染LncRNA OSER1-AS1-siRNA及NC miR为si-OSER1-AS1+miR-NC组,转染LncRNA OSER1-AS1-siRNA及miR-433-3p抑制物为si-OSER1-AS1+miR-433-3p抑制物组。检测细胞增殖活力、凋亡率、增殖细胞核抗原(PCNA)及裂解型caspase-3(cleaved caspase-3)的表达水平,采用双荧光素酶报告基因实验验证LncRNA OSER1-AS1靶向miR-433-3p。结果HCC组织中LncRNA OSER1-AS1的表达水平高于癌旁组织(1.77±0.34 vs1.00±0.21)、miR-433-3p的表达水平低于癌旁组织(0.65±0.09 vs 1.00±0.28)(P<0.05)且LncRNA OSER1-AS1与miR-433-3p呈负相关(r=-0.351,P<0.05);HCC细胞株中LncRNA OSER1-AS1的表达水平高于HL-7702细胞、miR-433-3p的表达水平低于HL-7702细胞(P<0.05)且MHCC97H细胞中上述变化最显著。si-OSER1-AS1组MHCC97H细胞中LncRNA OSER1-AS1、PCNA的表达水平及增殖活力低于si-NC组(0.37±0.05 vs 1.00±0.11,0.33±0.05 vs 0.92±0.12,0.51±0.09 vs 1.03±0.12),miR-433-3p、cleaved caspase-3的表达水平及凋亡率高于si-NC组(1.88±0.25 vs 1.00±0.09,0.96±0.11 vs 0.44±0.06,9.39%±1.15%vs 3.82%±0.55%)(P<0.05);si-OSER1-AS1+miR-433-3p抑制物组MHCC97H细胞中cleaved caspase-3表达水平及凋亡率低于si-OSER1-AS1+miR-NC组(0.27±0.05 vs 0.91±0.10,6.04%±0.77%vs 11.32%±1.32%),PCNA的表达水平及增殖活力高于si-OSER1-AS1+miR-NC组(0.94±0.12 vs 0.48±0.06,0.95±0.11 vs 0.34±0.05)(P<0.05)。结论LncRNA OSER1-AS1靶向miR-433-3p调控HCC细胞的增殖和凋亡。
