Vitamin C increases 5-hydroxymethylcytosine level and inhibits the growth of bladder cancer.
Vitamin C increases 5-hydroxymethylcytosine level and inhibits the growth of bladder cancer.
复制标题
维生素 C 增加 5-羟甲基胞嘧啶水平并抑制膀胱癌的生长
DOI：
10.1186/s13148-018-0527-7
复制
发表时间：
2018-07-13
影响因子：
5.7
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Peng D;Ge G;Gong Y;Zhan Y;He S;Guan B;Li Y;Xu Z;Hao H;He Z;Xiong G;Zhang C;Shi Y;Zhou Y;Ci W;Li X;Zhou L
背景：5-羟甲基胞嘧啶（5hmC）是由5-甲基胞嘧啶（5mC）转化为一组被称为10 - 11易位（TET）家族双加氧酶的酶。5hmC的丢失已被确定为大多数类型癌症的标志，并与肿瘤发生和进展有关。然而，5hmC在膀胱癌中的作用很少被研究。最近有报道称，维生素C作为TET双加氧酶的辅助因子可诱导5hmC的生成。在本研究中，我们探讨了5hmC在膀胱癌中的作用，以及维生素C增加5hmC模式的治疗效果。结果膀胱癌标本中5hmc降低，与患者总生存期有关。对肿瘤组织和维生素C处理的膀胱癌细胞中5hmC的全基因组定位显示，5hmC缺失在癌症相关基因中富集，维生素C处理相应增加了5hmC水平。在体外细胞系和体内异种移植物中，维生素C治疗改变了转录组并抑制了与膀胱癌细胞相关的恶性表型。结论本研究提供了膀胱癌中5hmC丢失的机制见解，并为探索维生素C作为膀胱癌潜在表观遗传治疗的治疗应用提供了理论依据。
Background5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is related to tumorigenesis and progression. However, the role of 5hmC in bladder cancer is seldom investigated. Vitamin C was recently reported to induce the generation of 5hmC by acting as a cofactor for TET dioxygenases. In this study, we explored the role of 5hmC in bladder cancer and the therapeutic efficacy of vitamin C in increasing the 5hmC pattern.Results5hmC was decreased in bladder cancer samples and was related to patient overall survival. Genome-wide mapping of 5hmC in tumor tissues and vitamin C-treated bladder cancer cells revealed that 5hmC loss was enriched in cancer-related genes and that vitamin C treatment increased 5hmC levels correspondingly. Vitamin C treatment shifted the transcriptome and inhibited the malignant phenotypes associated with bladder cancer cells in both in vitro cell lines and in vivo xenografts.ConclusionsThis study provided mechanistic insights regarding the 5hmC loss in bladder cancer and a rationale for exploring the therapeutic use of vitamin C as a potential epigenetic treatment for bladder cancer.
登录
查看更多内容
DOI：
10.1073/pnas.1612262113
发表时间：
2016-09-13
影响因子：
11.1
作者：
Liu, Minmin;Ohtani, Hitoshi;Jones, Peter A.
通讯作者：
Jones, Peter A.
影响因子：
5.2
作者：
He, Xi-Biao;Kim, Mirang;Kim, Seon-Young;Yi, Sang-Hoon;Rhee, Yong-Hee;Kim, Taeho;Lee, Eun-Hye;Park, Chang-Hwan;Dixit, Shilpy;Harrison, Fiona E.;Lee, Sang-Hun
通讯作者：
Lee, Sang-Hun
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
通过维生素C治疗对黑色素瘤细胞的表观遗传重编程。
影响因子：
5.7
作者：
Gustafson CB;Yang C;Dickson KM;Shao H;Van Booven D;Harbour JW;Liu ZJ;Wang G
通讯作者：
Wang G
影响因子：
64.8
作者：
Agathocleous M;Meacham CE;Burgess RJ;Piskounova E;Zhao Z;Crane GM;Cowin BL;Bruner E;Murphy MM;Chen W;Spangrude GJ;Hu Z;DeBerardinis RJ;Morrison SJ
通讯作者：
Morrison SJ