CXXC finger protein 1 (CFP1) bridges the reshaping of genomic H3K4me3 signature to the advancement of lung adenocarcinoma.
CXXC finger protein 1 (CFP1) bridges the reshaping of genomic H3K4me3 signature to the advancement of lung adenocarcinoma.
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DOI：
10.1038/s41392-023-01612-3
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发表时间：
2023-09-21
影响因子：
39.3
通讯作者：
He, Jie
中科院分区：
文献类型：
--
作者：
Fan, Tao;Xiao, Chu;Liu, Hengchang;Liu, Yu;Wang, Liyu;Tian, He;Li, Chunxiang;He, Jie
组蛋白H3赖氨酸4三甲基化（H3 K4 me 3）是一种典型的染色质修饰，与基因转录活性相关，在调节各种细胞功能中起着关键作用。H3 K4 me 3甲基转移酶复合物的组分，称为与SET 1（COMPASS）相关的蛋白质，已经涉及通过诱导H3 K4 me 3修饰发挥癌症保护或癌症抑制作用。然而，COMPASS CXXC型锌指蛋白1（CFP 1）在恶性进展中不可或缺的非催化成分的作用仍不清楚。我们已经通过体外和体内模型揭示了CFP 1促进肺腺癌（LUAD）细胞增殖、迁移和侵袭，同时损害细胞凋亡。此外，CFP 1高表达被确定为在多个公共和内部LUAD数据集中出现的不良预后指标。值得注意的是，CFP 1缺陷导致对癌细胞转录组的双重影响，包括癌症促进因子的广泛失活以及癌症抑制因子的激活。结合染色质免疫沉淀测序（ChIP-seq）分析，我们发现CFP 1消融重塑了基因组H3 K4 me 3分布特征，对TGF-β和WNT信号通路有显著影响。总的来说，我们的研究提出CFP 1通过基因组组蛋白甲基化重编程介导肿瘤发生，为未来研究癌症进展中的表观遗传修饰和潜在的治疗进展提供了见解。
Histone H3 lysine 4 trimethylation (H3K4me3) is a canonical chromatin modification associated with active gene transcription, playing a pivotal role in regulating various cellular functions. Components of the H3K4me3 methyltransferase complex, known as the proteins associated with SET1 (COMPASS), have been implicated in exerting cancer-protective or cancer-inhibitory effects through inducive H3K4me3 modification. However, the role of the indispensable non-catalytic component of COMPASS CXXC-type zinc finger protein 1 (CFP1) in malignant progression remains unclear. We have unveiled that CFP1 promote lung adenocarcinoma (LUAD) cell proliferation, migration, and invasion while impairing cell apoptosis through in vitro and in vivo models. In addition, high CFP1 expression was identified as emerged as an adverse prognostic indicator across multiple public and in-house LUAD datasets. Notably, CFP1 deficiency led to dual effects on cancer cell transcriptome including extensive inactivation of cancer-promoting as well as activation of cancer repressors. Combining this with the chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we showed that CFP1 ablation reshaped the genomic H3K4me3 distribution signature, with prominent effects on TGF-β and WNT signaling pathways. Collectively, our study proposes that CFP1 mediates tumorigenesis by genomic histone methylation reprogramming, offering insights for future investigations into epigenetic modifications in cancer progression and potential therapeutic advancements.
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影响因子：
9
作者：
Li Y;Yuan R;Ren T;Yang B;Miao H;Liu L;Li Y;Cai C;Yang Y;Hu Y;Jiang C;Xu Q;Zhang Y;Liu Y
通讯作者：
Liu Y
KCNMA1与PTK2协同作用是胃癌的新型抑癌基因，与疾病结局相关
影响因子：
37.3
作者：
Ma, Gaoxiang;Liu, Hanting;Chu, Haiyan
通讯作者：
Chu, Haiyan
影响因子：
30.8
作者：
Douillet D;Sze CC;Ryan C;Piunti A;Shah AP;Ugarenko M;Marshall SA;Rendleman EJ;Zha D;Helmin KA;Zhao Z;Cao K;Morgan MA;Singer BD;Bartom ET;Smith ER;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
4.8
作者：
Lee, JH;Skalnik, DG
通讯作者：
Skalnik, DG
DOI：
10.1073/pnas.2122245119
发表时间：
2022-03-22
影响因子：
11.1
作者：
Huang Y;Du S;Liu J;Huang W;Liu W;Zhang M;Li N;Wang R;Wu J;Chen W;Jiang M;Zhou T;Cao J;Yang J;Huang L;Gu A;Niu J;Cao Y;Zong WX;Wang X;Liu J;Qian K;Wang H
通讯作者：
Wang H