Histone acetyltransferase CSRP2BP promotes the epithelial-mesenchymal transition and metastasis of cervical cancer cells by activating N-cadherin.
Histone acetyltransferase CSRP2BP promotes the epithelial-mesenchymal transition and metastasis of cervical cancer cells by activating N-cadherin.
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DOI：
10.1186/s13046-023-02839-2
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发表时间：
2023-10-17
影响因子：
11.3
通讯作者：
Ma, Yanlin
中科院分区：
文献类型：
--
作者：
Yang, Xiaohui;Sun, Fei;Gao, Yueying;Li, Mengyongwei;Liu, Mian;Wei, Yunjian;Jie, Qiuling;Wang, Yibing;Mei, Jiaoqi;Mei, Jingjing;Ma, Linna;Shi, Yuechuan;Chen, Manling;Li, Yongsheng;Li, Qi;Liu, Mingyao;Ma, Yanlin
异常的上皮-间充质转化(EMT)参与了宫颈癌的转移，并与组蛋白乙酰化有关。然而，组蛋白乙酰化在宫颈癌EMT和转移中的潜在分子机制仍然不清楚。我们系统地研究了组蛋白乙酰化基因在宫颈癌中的表达模式及其与EMT通路的相关性。用Western blotting和免疫组织化学方法检测CSRP2BP在宫颈癌组织和细胞系中的表达。通过细胞生长曲线、EDU比色法、流式细胞仪和异种移植实验检测CSRP2BP对宫颈癌细胞增殖和致瘤性的影响。采用创面愈合实验、跨膜迁移实验和肺转移模型观察CSRP2BP对宫颈癌细胞侵袭转移的影响。采用RNA-SEQ、染色质免疫沉淀(ChIP)、共免疫沉淀(Co-IP)和荧光素酶报告基因分析等方法，揭示CSRP2BP促进宫颈癌EMT和转移的分子机制。我们优先考虑组蛋白乙酰转移酶，CSRP2BP，作为宫颈癌EMT和转移的关键角色。CSRP2BP在宫颈癌组织中的表达明显升高，且高表达与预后不良有关。CSRP2BP的过表达在体内外均促进宫颈癌细胞的增殖和转移，而CSRP2BP的过表达则具有相反的作用。此外，CSRP2BP还增加了对顺铂化疗的耐药性。在机制上，CSRP2BP介导组蛋白4在5和12位赖氨酸乙酰化，与转录因子Smad4协同结合N-钙粘蛋白基因启动子中的SEB2序列，上调N-钙粘蛋白的转录。因此，CSRP2BP通过激活N-钙粘蛋白促进宫颈癌细胞的EMT和转移。本研究表明组蛋白乙酰转移酶CSRP2BP部分通过增加EMT促进宫颈癌转移，提示CSRP2BP可作为预测预后的指标和抗宫颈癌转移的潜在治疗靶点。网上版载有补充材料，可在10.1186/s13046-023-02839-2查阅。
Dysregulated epithelial–mesenchymal transition (EMT) is involved in cervical cancer metastasis and associated with histone acetylation. However, the underlying molecular mechanisms of histone acetylation in cervical cancer EMT and metastasis are still elusive. We systematically investigated the expression patterns of histone acetylation genes and their correlations with the EMT pathway in cervical cancer. The expression of CSRP2BP among cervical cancer tissues and cell lines was detected using Western blotting and immunohistochemistry analyses. The effects of CSRP2BP on cervical cancer cell proliferation and tumorigenicity were examined by cell growth curve, EdU assay, flow cytometry and xenotransplantation assays. Wound healing assays, transwell migration assays and pulmonary metastasis model were used to evaluate the effects of CSRP2BP on cell invasion and metastasis of cervical cancer cells in vivo and in vitro. RNA-seq, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter assays were used to uncover the molecular mechanisms of CSRP2BP in promoting cervical cancer EMT and metastasis. We prioritized a top candidate histone acetyltransferase, CSRP2BP, as a key player in cervical cancer EMT and metastasis. The expression of CSRP2BP was significantly increased in cervical cancer tissues and high CSRP2BP expression was associated with poor prognosis. Overexpression of CSRP2BP promoted cervical cancer cell proliferation and metastasis both in vitro and in vivo, while knockdown of CSRP2BP obtained the opposite effects. In addition, CSRP2BP promoted resistance to cisplatin chemotherapy. Mechanistically, CSRP2BP mediated histone 4 acetylation at lysine sites 5 and 12, cooperated with the transcription factor SMAD4 to bind to the SEB2 sequence in the N-cadherin gene promotor and upregulated N-cadherin transcription. Consequently, CSRP2BP promoted cervical cancer cell EMT and metastasis through activating N-cadherin. This study demonstrates that the histone acetyltransferase CSRP2BP promotes cervical cancer metastasis partially through increasing the EMT and suggests that CSRP2BP could be a prognostic marker and a potential therapeutic target for combating cervical cancer metastasis. The online version contains supplementary material available at 10.1186/s13046-023-02839-2.
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p300 通过诱导非小细胞肺癌细胞上皮间质转化促进增殖、迁移和侵袭
影响因子：
3.8
作者：
Hou X;Gong R;Zhan J;Zhou T;Ma Y;Zhao Y;Zhang Y;Chen G;Zhang Z;Ma S;Chen X;Gao F;Hong S;Luo F;Fang W;Yang Y;Huang Y;Chen L;Yang H;Zhang L
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Zhang L
DOI：
10.26355/eurrev_202101_24631
发表时间：
2021-01-01
影响因子：
3.3
作者：
Liang, B-Q;Zhou, S-G;Zhu, X.
通讯作者：
Zhu, X.
DOI：
10.15252/embj.2021108647
发表时间：
2021-09-15
期刊：
The EMBO journal
影响因子：
--
作者：
Brabletz S;Schuhwerk H;Brabletz T;Stemmler MP
通讯作者：
Stemmler MP
DICER1 通过组蛋白乙酰化和甲基化调节子宫内膜癌侵袭。
影响因子：
3.9
作者：
Li B;Lu W;Qu J;Zhang Y;Wan X
通讯作者：
Wan X
影响因子：
8
作者：
Baldus, SE;Schwarz, E;Schwarte-Waldhoff, I
通讯作者：
Schwarte-Waldhoff, I