RNA编辑酶腺苷脱氨酶1(adenosine deaminase acting on RNA 1,ADAR1)在肿瘤领域中的研究备受关注,包括前列腺癌。作为第一个被发现的腺苷转变为肌苷(adenosine to inosine,A-to-I)RNA编辑酶,ADAR1在肿瘤免疫逃逸的研究越来越多。因此,...RNA编辑酶腺苷脱氨酶1(adenosine deaminase acting on RNA 1,ADAR1)在肿瘤领域中的研究备受关注,包括前列腺癌。作为第一个被发现的腺苷转变为肌苷(adenosine to inosine,A-to-I)RNA编辑酶,ADAR1在肿瘤免疫逃逸的研究越来越多。因此,本文对ADAR1的作用机制及其在前列腺癌肿瘤免疫作用综述,为挖掘ADAR1在前列腺癌中作为潜在诊治靶点提供有益总结。展开更多
Z-DNA binding protein 1(ZBP1)has emerged as a critical player in cancer biology,functioning as a cytosolic nucleic acid sensor that triggers PANoptosis,a form of programmed cell death that integrates pyroptosis,apopto...Z-DNA binding protein 1(ZBP1)has emerged as a critical player in cancer biology,functioning as a cytosolic nucleic acid sensor that triggers PANoptosis,a form of programmed cell death that integrates pyroptosis,apoptosis,and necroptosis.Although ZBP1 was initially recognized for its role in antiviral defense,recent research has highlighted its importance in the tumor microenvironment(TME),where it is essential for suppressing tumor growth and proliferation.This review explores the multifaceted role of ZBP1 in various cancer types,emphasizing its ability to detect Z-nucleic acids and double-stranded RNAs,leading to the initiation of PANoptosis through receptorinteracting protein homotypic interaction motif(RHIM)-dependent interactions.However,the antitumor potential of ZBP1 involves adenosine deaminase RNA specific 1(ADAR1),particularly its ADAR1-P150 isoform(150 kDa),which inhibits ZBP1-mediated cell death,thereby promoting tumor progression.This has spurred interest in the development of ADAR1 inhibitors and combination therapies with US Food and Drug Administration(FDA)-approved agents such as interferon-α(IFN-α)to increase ZBP1 activity.Promising studies have demonstrated that ZBP1 regulation can significantly impact tumor suppression,particularly in necrotic tumors,where its expression is correlated with reduced tumor growth.Furthermore,oligomerization of telomeric repeat-containing RNA(TERRA)-bound ZBP1 on the mitochondrial membrane has been linked to mitochondrial antiviral signaling(MAVS)-induced interferon responses,adding another layer to the tumor-suppressive functions of ZBP1.Clinical investigations into nuclear export inhibitors(NEIs)such as KPT-330 and KPT-8602,in combination with IFN therapy,have shown potential in harnessing ZBP1 to induce PANoptosis and suppress tumor growth.Additionally,the small molecule curaxin CBL0137 has been identified as a promising agent for reversing immune checkpoint blockade(ICB)resistance by inducing Z-DNA(Z form DNA)formation and ZBP1-mediated necroptosis in tumor fibroblasts.This review consolidates recent advancements in ZBP1 research,highlighting its therapeutic potential as a target for cancer treatment and its promising role in overcoming resistance to existing therapies.展开更多
旨在克隆猪作用于RNA的腺苷脱氨酶1基因(ADAR1)cDNA全长序列,检测该基因在大白猪不同组织及不同日龄背膘中的表达情况。本研究利用RACE(rapid-amplification of cDNA ends)克隆大白猪ADAR1基因mRNA全长序列,并对其进行生物信息学分析;...旨在克隆猪作用于RNA的腺苷脱氨酶1基因(ADAR1)cDNA全长序列,检测该基因在大白猪不同组织及不同日龄背膘中的表达情况。本研究利用RACE(rapid-amplification of cDNA ends)克隆大白猪ADAR1基因mRNA全长序列,并对其进行生物信息学分析;采用荧光定量PCR方法检测ADAR1在不同组织中的表达水平,并探究不同日龄背膘中ADAR1的表达规律。结果表明,猪ADAR1基因cDNA全长6259bp,编码1145个氨基酸,与人、黑猩猩、猕猴、长臂猿、黄牛、山羊和绵羊的氨基酸序列一致性均不低于85%。该基因编码的蛋白具有2个Zα结合结构域,3个双链RNA结合结构域和1个脱氨酶结构域。ADAR1在心、肝、脾、肺、肾、脑、肌肉、小肠和背部脂肪组织以及7、60、120和180日龄个体背膘组织中均表达,其表达量总体上表现出随个体发育先下降后上升的趋势。综上所述,本研究成功克隆了猪ADAR1基因cDNA全长序列,发现其在猪体内广泛表达,并且在不同日龄猪背膘组织中表达水平存在差异,为今后深入研究ADAR1的功能奠定了理论基础。展开更多
文摘RNA编辑酶腺苷脱氨酶1(adenosine deaminase acting on RNA 1,ADAR1)在肿瘤领域中的研究备受关注,包括前列腺癌。作为第一个被发现的腺苷转变为肌苷(adenosine to inosine,A-to-I)RNA编辑酶,ADAR1在肿瘤免疫逃逸的研究越来越多。因此,本文对ADAR1的作用机制及其在前列腺癌肿瘤免疫作用综述,为挖掘ADAR1在前列腺癌中作为潜在诊治靶点提供有益总结。
基金supported by the National Natural Science Foundation of China under Grant 22376100.
文摘Z-DNA binding protein 1(ZBP1)has emerged as a critical player in cancer biology,functioning as a cytosolic nucleic acid sensor that triggers PANoptosis,a form of programmed cell death that integrates pyroptosis,apoptosis,and necroptosis.Although ZBP1 was initially recognized for its role in antiviral defense,recent research has highlighted its importance in the tumor microenvironment(TME),where it is essential for suppressing tumor growth and proliferation.This review explores the multifaceted role of ZBP1 in various cancer types,emphasizing its ability to detect Z-nucleic acids and double-stranded RNAs,leading to the initiation of PANoptosis through receptorinteracting protein homotypic interaction motif(RHIM)-dependent interactions.However,the antitumor potential of ZBP1 involves adenosine deaminase RNA specific 1(ADAR1),particularly its ADAR1-P150 isoform(150 kDa),which inhibits ZBP1-mediated cell death,thereby promoting tumor progression.This has spurred interest in the development of ADAR1 inhibitors and combination therapies with US Food and Drug Administration(FDA)-approved agents such as interferon-α(IFN-α)to increase ZBP1 activity.Promising studies have demonstrated that ZBP1 regulation can significantly impact tumor suppression,particularly in necrotic tumors,where its expression is correlated with reduced tumor growth.Furthermore,oligomerization of telomeric repeat-containing RNA(TERRA)-bound ZBP1 on the mitochondrial membrane has been linked to mitochondrial antiviral signaling(MAVS)-induced interferon responses,adding another layer to the tumor-suppressive functions of ZBP1.Clinical investigations into nuclear export inhibitors(NEIs)such as KPT-330 and KPT-8602,in combination with IFN therapy,have shown potential in harnessing ZBP1 to induce PANoptosis and suppress tumor growth.Additionally,the small molecule curaxin CBL0137 has been identified as a promising agent for reversing immune checkpoint blockade(ICB)resistance by inducing Z-DNA(Z form DNA)formation and ZBP1-mediated necroptosis in tumor fibroblasts.This review consolidates recent advancements in ZBP1 research,highlighting its therapeutic potential as a target for cancer treatment and its promising role in overcoming resistance to existing therapies.
文摘旨在克隆猪作用于RNA的腺苷脱氨酶1基因(ADAR1)cDNA全长序列,检测该基因在大白猪不同组织及不同日龄背膘中的表达情况。本研究利用RACE(rapid-amplification of cDNA ends)克隆大白猪ADAR1基因mRNA全长序列,并对其进行生物信息学分析;采用荧光定量PCR方法检测ADAR1在不同组织中的表达水平,并探究不同日龄背膘中ADAR1的表达规律。结果表明,猪ADAR1基因cDNA全长6259bp,编码1145个氨基酸,与人、黑猩猩、猕猴、长臂猿、黄牛、山羊和绵羊的氨基酸序列一致性均不低于85%。该基因编码的蛋白具有2个Zα结合结构域,3个双链RNA结合结构域和1个脱氨酶结构域。ADAR1在心、肝、脾、肺、肾、脑、肌肉、小肠和背部脂肪组织以及7、60、120和180日龄个体背膘组织中均表达,其表达量总体上表现出随个体发育先下降后上升的趋势。综上所述,本研究成功克隆了猪ADAR1基因cDNA全长序列,发现其在猪体内广泛表达,并且在不同日龄猪背膘组织中表达水平存在差异,为今后深入研究ADAR1的功能奠定了理论基础。
