p53 is a transcription factor that governs numerous stress response pathways within the ceil. Maintaining the right levels of p53 is crucial for ceil survival and proper cellular homeostasis, The tight regulation of p...p53 is a transcription factor that governs numerous stress response pathways within the ceil. Maintaining the right levels of p53 is crucial for ceil survival and proper cellular homeostasis, The tight regulation of p53 involves many cellular components, most notably its major negative regulators Mdm2 and Mdm4, which maintain p53 protein amount and activity in tight check, microRNAs （miRNAs） are small non-coding RNAs that target specific mRNAs to translational arrest and degradation, miRNAs are also key compo- nents of the normal p53 pathway, joining forces with Mdm2 and Mdm4 to maintain proper p53 activity. Here we review the current knowledge of miRNAs targeting Mdm2 and Mdm4, and their importance in different tissues and in pathological states such as cancer. In addition, we address the role of Alu sequences-highly abundant retroelements spread throughout the human genome, and their impact on gene regulation via the miRNA machinery. Aius occupy a significant portion of genes＇ 31UTR, and as such they have the potential to impact mRNA regulation. Since Alus are primate-specific, they introduce a new regulatory layer into primate genomes. Atus can influence and alter gene regulation, creating primate-specific cancer-preventive regulatory mechanisms to sustain the transition to longer life span in primates. We review the possible influence of Alu sequences on miRNA functionality in general and specifically within the p53 network.展开更多
文摘目的探讨错配修复基因(h MLH1)、RAS相关区域家族1A基因(RASSF1A)启动子区甲基化以及ALU基因甲基化水平与肾细胞癌(肾癌)的关系。方法巢式甲基化特异性PCR(n MSP)检测15例肾癌组织及其相应癌旁组织中h MLH1、RASSF1A基因启动子区的甲基化状态,联合亚硫酸氢钠限制酶分析方法(COBRA)分析ALU基因甲基化水平。结果 h MLH1基因在肾癌组织中的甲基化率(0.41±0.18)%高于癌旁组织(0.32±0.13)%,差异有统计学意义(t=2.52,P<0.05);ALU基因在癌组织中的甲基化率(0.11±0.04)%低于癌旁组织(0.12±0.03)%,差异有统计学意义(t=3.82,P<0.05)。而RASSF1A基因在肾癌组织和癌旁组织中的甲基化率分别为(0.75±0.11)%和(0.69±0.12)%,差异无统计学意义(t=1.35,P>0.05)。结论 h MLH1基因启动子区甲基化以及ALU基因甲基化可能与肾癌的发病有关,RASSF1A基因启动子区甲基化与肾癌发病无关。
文摘p53 is a transcription factor that governs numerous stress response pathways within the ceil. Maintaining the right levels of p53 is crucial for ceil survival and proper cellular homeostasis, The tight regulation of p53 involves many cellular components, most notably its major negative regulators Mdm2 and Mdm4, which maintain p53 protein amount and activity in tight check, microRNAs （miRNAs） are small non-coding RNAs that target specific mRNAs to translational arrest and degradation, miRNAs are also key compo- nents of the normal p53 pathway, joining forces with Mdm2 and Mdm4 to maintain proper p53 activity. Here we review the current knowledge of miRNAs targeting Mdm2 and Mdm4, and their importance in different tissues and in pathological states such as cancer. In addition, we address the role of Alu sequences-highly abundant retroelements spread throughout the human genome, and their impact on gene regulation via the miRNA machinery. Aius occupy a significant portion of genes＇ 31UTR, and as such they have the potential to impact mRNA regulation. Since Alus are primate-specific, they introduce a new regulatory layer into primate genomes. Atus can influence and alter gene regulation, creating primate-specific cancer-preventive regulatory mechanisms to sustain the transition to longer life span in primates. We review the possible influence of Alu sequences on miRNA functionality in general and specifically within the p53 network.
