MG149通过抑制赖氨酸乙酰转移酶kat5介导的c-Myc乙酰化来抑制间变性甲状腺癌的进展。

IF 1.1 4区医学 Q4 ONCOLOGY

Bulletin Du Cancer Pub Date : 2025-02-01 DOI:10.1016/j.bulcan.2024.11.008

Pan Sheng , Zhen Chen , Junjun Wen , Chuanming Tong , Ju Wang , Zhengwen Du

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引用次数: 0

摘要

背景：间变性甲状腺癌（ATC）是一种高致死率的甲状腺癌。先前的研究发现，赖氨酸乙酰转移酶5 （KAT5）通过稳定c-Myc促进ATC的发展。因此，我们设计了实验来证实KAT5抑制剂（MG149）在ATC中的抗肿瘤作用。方法：Western blotting检测ATC细胞和异种移植肿瘤组织中KAT5、c-Myc和上皮-间质转化（epithelial-mesenchymal transition， EMT）相关蛋白的表达水平。细胞计数试剂盒-8、流式细胞术、伤口愈合和transwell实验显示MG149对ATC细胞系细胞增殖、凋亡、迁移和侵袭的影响。免疫荧光法检测ATC细胞株E-cadherin和N-cadherin水平。采用共免疫沉淀法检测MG149对kat5介导的c-Myc稳定的影响。评估ATC异种移植模型的肿瘤体积和肿瘤重量。H&E染色显示MG149对体内肺转移的影响。我们进一步研究MG149是否能增强ATC对顺铂（CDDP）的敏感性。结果：MG149抑制细胞增殖，增加细胞凋亡。MG149抑制ATC细胞的迁移和侵袭能力。MG149显著抑制CAL-62和8505C细胞的EMT。MG149抑制kat5介导的c-Myc乙酰化。MG149在体内抑制肿瘤生长和肺转移。此外，MG149在体外和体内增强了ATC细胞对CDDP的敏感性。结论：MG149通过抑制KAT5介导的c-Myc乙酰化而抑制ATC的进展和转移。

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MG149 suppresses anaplastic thyroid cancer progression by inhibition of lysine acetyltransferase KAT5-mediated c-Myc acetylation

Background

Anaplastic thyroid cancer (ATC) is a highly lethal form of thyroid cancer. lysine acetyltransferase 5 (KAT5) has been found to promote ATC development via c-Myc stabilization by previous study. We thus designed experiments to confirm the anti-tumor effect of a KAT5 inhibitor (MG149) in ATC.

Methods

Western blotting assessed the level of KAT5, c-Myc, and epithelial-mesenchymal transition (EMT)-related proteins in ATC cells and xenograft tumor tissues. Cell counting kit-8, flow cytometry, wound healing, and transwell assays revealed the effect of MG149 on cell proliferation, apoptosis, migration, and invasion in ATC cell lines. Immunofluorescence detected the level of E-cadherin and N-cadherin in ATC cell lines. The effect of MG149 on KAT5-mediated c-Myc stabilization was detected using co-immunoprecipitation assay. Tumor volume and tumor weight in ATC xenograft models were evaluated. H&E staining showed the effect of MG149 on lung metastasis in vivo. We further investigated whether MG149 can enhance the sensitivity of ATC to cisplatin (CDDP).

Results

MG149 inhibited cell proliferation and increased the apoptosis of cells. MG149 suppressed the migratory and invasive ability of ATC cells. The EMT in CAL-62 and 8505 C cells was significantly inhibited by MG149. MG149 suppressed the KAT5-mediated c-Myc acetylation. MG149 inhibited tumor growth and lung metastasis in vivo. Additionally, MG149 potentiated the sensitivity to CDDP in ATC cells in vitro and in vivo.

Conclusion

MG149 suppresses ATC progression and metastasis by inhibiting the acetylation of c-Myc mediated by KAT5.

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来源期刊

Bulletin Du Cancer 医学-肿瘤学

CiteScore

1.90

自引率

16.70%

发文量

224

审稿时长

37 days

期刊介绍： Without doubt, the ''Bulletin du Cancer'' is the French language publication of reference in the field of cancerology. Official organ of the French Society of Cancer, this journal covers all the information available, whether in the form of original articles or review articles, but also clinical cases and letters to the editor, including various disciplines as onco-hematology, solids tumors, medical oncology, pharmacology, epidemiology, biology as well as fundamental research in cancerology. The journal proposes a clinical and therapeutic approach of high scientific standard and regular updates in knowledge are thus made possible. Articles can be submitted in French or English.