Huang Zhiang, Zhang Wanru, Wang Ping, Wu Mengyao, Guo Yipu, Chen Jingying
The First Affiliated Hospital, Henan University, Kaifeng 475004, China.
Joint National Laboratory for Antibody Drug Engineering, School of Medicine, Henan University, Kaifeng, China.
Transl Oncol. 2025 Jan;51:102218. doi: 10.1016/j.tranon.2024.102218. Epub 2024 Nov 27.
Lung cancer, particularly lung adenocarcinoma, poses a significant health challenge due to its high incidence and mortality rates. Despite advancements in targeted therapies, treatment outcomes for lung adenocarcinoma remain unsatisfactory. This study explores the role of the histone acetyltransferase MYST2 in lung adenocarcinoma and its potential as a therapeutic target.
An analysis using the TIMER 2.0 and TCGA databases was performed to compare the expression levels of MYST2 between lung adenocarcinoma tissues and normal tissues. Functional assays, including cell proliferation, migration, and invasion, were conducted to evaluate the effects of MYST2 overexpression and knockout in lung cancer cells. Co-immunoprecipitation and GST pull-down assays were utilized to identify interactions involving the MYST domain of MYST2 and p38, while also assessing the impact of MYST2 on the binding between MEK6 and p38.
The analysis revealed that MYST2 was significantly up-regulated in lung adenocarcinoma tissues compared to normal tissues and was associated with poor prognosis. Functional assays demonstrated that MYST2 overexpression promoted, whereas MYST2 knockout inhibited, lung cancer cell proliferation, migration, and invasion. Mechanistically, MYST2 enhanced the phosphorylation of p38 and ERK. Co-immunoprecipitation and GST pull-down assays identified the MYST domain of MYST2 as crucial for its interaction with p38. Additionally, MYST2 overexpression facilitated the binding of MEK6 to p38, indirectly influencing p38 activity.
These findings suggest that MYST2 acts as an oncogene in lung cancer by modulating p38 phosphorylation through the MYST domain, underscoring its potential as a prognostic marker and therapeutic target.
肺癌，尤其是肺腺癌，因其高发病率和死亡率对健康构成重大挑战。尽管靶向治疗取得了进展，但肺腺癌的治疗效果仍不尽人意。本研究探讨组蛋白乙酰转移酶MYST2在肺腺癌中的作用及其作为治疗靶点的潜力。
使用TIMER 2.0和TCGA数据库进行分析，比较肺腺癌组织和正常组织中MYST2的表达水平。进行了包括细胞增殖、迁移和侵袭在内的功能测定，以评估MYST2过表达和敲除对肺癌细胞的影响。利用免疫共沉淀和谷胱甘肽S-转移酶下拉实验来鉴定涉及MYST2的MYST结构域与p38之间的相互作用，同时评估MYST2对MEK6与p38结合的影响。
分析显示，与正常组织相比，肺腺癌组织中MYST2显著上调，且与预后不良相关。功能测定表明，MYST2过表达促进肺癌细胞增殖、迁移和侵袭，而MYST2敲除则抑制这些过程。机制上，MYST2增强了p38和ERK的磷酸化。免疫共沉淀和谷胱甘肽S-转移酶下拉实验确定MYST2的MYST结构域对其与p38的相互作用至关重要。此外，MYST2过表达促进了MEK6与p38的结合，间接影响p38活性。
这些发现表明，MYST2通过MYST结构域调节p38磷酸化，在肺癌中起癌基因作用，突出了其作为预后标志物和治疗靶点的潜力。
