胃癌是消化系统最常见的恶性肿瘤之一,多数患者发现时已处于晚期,预后不佳。外科手术及化学治疗(化疗仍是目前胃癌的主要治疗方式。N6-甲基腺嘌呤(N6-methyladenosine,m^(6)A)是近年来肿瘤研究的热点。m^(6)A作为真核生物中最常见的RNA...胃癌是消化系统最常见的恶性肿瘤之一,多数患者发现时已处于晚期,预后不佳。外科手术及化学治疗(化疗仍是目前胃癌的主要治疗方式。N6-甲基腺嘌呤(N6-methyladenosine,m^(6)A)是近年来肿瘤研究的热点。m^(6)A作为真核生物中最常见的RNA修饰形式,可以调控RNA循环的各个阶段,包括RNA剪接、加工、降解和翻译等,从而调控RNA的表达和功能,在细胞分化、发育和代谢等各个环节中发挥关键作用。m^(6)A去甲基化酶可去除RNA上的甲基基团,确保m^(6)A甲基化是一个动态的可逆的过程。作为m^(6)A甲基化过程的关键酶,m^(6)A去甲基化酶——脂肪和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)、AlkB同系物5(AlkB homolog 5,ALKBH5)、ALKBH3的失调能通过多种机制调控胃癌的演进过程,与胃癌的发生发展密切相关。m^(6)A去甲基化酶通过调节信号通路,改变胃癌细胞的增殖和侵袭能力,影响胃癌对化疗药物的耐药性,参与调控胃癌的免疫应答及线粒体代谢,从而影响胃癌细胞的生长,有望成为一个全新的治疗靶点。该文综述了m^(6)A去甲基化酶参与胃癌发生发展的分子机制,以及其表达和功能与胃癌生物学特性的关系,旨在为胃癌的早期诊断和靶向治疗提供新的研究思路。展开更多
ALKBH3,a demethylase responsible for demethylating N1-methyladenosine(m^(1)A)in mRNA and N1-methyldeoxyadenosine in single-stranded DNA,plays an important role in DNA repair and cancer cell proliferation.However,its f...ALKBH3,a demethylase responsible for demethylating N1-methyladenosine(m^(1)A)in mRNA and N1-methyldeoxyadenosine in single-stranded DNA,plays an important role in DNA repair and cancer cell proliferation.However,its function in hematopoietic stem cells(HSCs)is unknown.In this study,we generated Alkbh3 knockout mice and observed that the deletion of Alkbh3 does not impair the reconstitution capacity of HSCs in both primary and secondary transplantation.Aged hematopoietic stem and progenitor cells exhibit increased expression of ALKBH3.Forced ALKBH3 rescued the differentiation skewing without affecting the reconstitution capacity of aged HSCs.In brief,our study for the first time investigated the functional role of ALKBH3 in hematopoietic system,and observed that ALKBH3 is dispensable for HSCs maintenance and differentiation,but overexpression of ALKBH3 rectified the differentiation skewing of aged HSCs.展开更多
文摘胃癌是消化系统最常见的恶性肿瘤之一,多数患者发现时已处于晚期,预后不佳。外科手术及化学治疗(化疗仍是目前胃癌的主要治疗方式。N6-甲基腺嘌呤(N6-methyladenosine,m^(6)A)是近年来肿瘤研究的热点。m^(6)A作为真核生物中最常见的RNA修饰形式,可以调控RNA循环的各个阶段,包括RNA剪接、加工、降解和翻译等,从而调控RNA的表达和功能,在细胞分化、发育和代谢等各个环节中发挥关键作用。m^(6)A去甲基化酶可去除RNA上的甲基基团,确保m^(6)A甲基化是一个动态的可逆的过程。作为m^(6)A甲基化过程的关键酶,m^(6)A去甲基化酶——脂肪和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)、AlkB同系物5(AlkB homolog 5,ALKBH5)、ALKBH3的失调能通过多种机制调控胃癌的演进过程,与胃癌的发生发展密切相关。m^(6)A去甲基化酶通过调节信号通路,改变胃癌细胞的增殖和侵袭能力,影响胃癌对化疗药物的耐药性,参与调控胃癌的免疫应答及线粒体代谢,从而影响胃癌细胞的生长,有望成为一个全新的治疗靶点。该文综述了m^(6)A去甲基化酶参与胃癌发生发展的分子机制,以及其表达和功能与胃癌生物学特性的关系,旨在为胃癌的早期诊断和靶向治疗提供新的研究思路。
基金This work was supported by grant numbers 2018YFA0800200,2017YFA0104000,Z181100001818005 and 91849106 to J.WW.,from the National KeyR&D Program of China or the Beijing Municipal Science&Technology Commission and the National Natural Science Foundation of China.
文摘ALKBH3,a demethylase responsible for demethylating N1-methyladenosine(m^(1)A)in mRNA and N1-methyldeoxyadenosine in single-stranded DNA,plays an important role in DNA repair and cancer cell proliferation.However,its function in hematopoietic stem cells(HSCs)is unknown.In this study,we generated Alkbh3 knockout mice and observed that the deletion of Alkbh3 does not impair the reconstitution capacity of HSCs in both primary and secondary transplantation.Aged hematopoietic stem and progenitor cells exhibit increased expression of ALKBH3.Forced ALKBH3 rescued the differentiation skewing without affecting the reconstitution capacity of aged HSCs.In brief,our study for the first time investigated the functional role of ALKBH3 in hematopoietic system,and observed that ALKBH3 is dispensable for HSCs maintenance and differentiation,but overexpression of ALKBH3 rectified the differentiation skewing of aged HSCs.
