MK2-mediated AKT/MYC signaling activation promotes epithelial-mesenchymal transition in lung adenocarcinoma.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-09-25 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1615018

Rong Qi, Chen Fang, Penghui Liu, Weiguo Gu, Chao Shi, Guohua Zhang, Feng Qiu

{"title":"MK2-mediated AKT/MYC signaling activation promotes epithelial-mesenchymal transition in lung adenocarcinoma.","authors":"Rong Qi, Chen Fang, Penghui Liu, Weiguo Gu, Chao Shi, Guohua Zhang, Feng Qiu","doi":"10.3389/fgene.2025.1615018","DOIUrl":null,"url":null,"abstract":"Purpose: The protein kinase Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) is linked to higher risks of metastasis and mortality in some cancers. Nonetheless, its precise function in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore MK2's function in LUAD cells and identify the underlying molecular mechanisms.Methods: MK2 expression in LUAD patients was confirmed through Timer2.0 database and tissue microarrays. Immunohistochemical staining for MK2 was performed on LUAD samples to investigate its association with metastasis and invasion. The activity of MK2 was inhibited in LUAD cell lines A549 and H358 using a specific MK2 inhibitor. Subsequently, cell viability, migration, and invasion were assessed. Gene expression changes were confirmed through Western blotting. Additionally, an AKT activator was used to validate the role of the MK2-regulated AKT/MYC signaling pathway.Results: MK2 expression is significantly higher in LUAD tissues compared to adjacent normal tissues. Reducing MK2 activity not only curtails cell proliferation, migration, and EMT-related invasion in vitro but also disrupts the AKT/MYC signaling axis. Activation of the AKT/MYC pathway can counteract the inhibitory effects of MK2 suppression.Conclusion: Our findings suggest that MK2 promotes migration and invasion in LUAD through the AKT/MYC signaling pathways, positioning MK2 as a potential therapeutic target in LUAD treatment.","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1615018"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507368/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fgene.2025.1615018","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: The protein kinase Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) is linked to higher risks of metastasis and mortality in some cancers. Nonetheless, its precise function in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore MK2's function in LUAD cells and identify the underlying molecular mechanisms.

Methods: MK2 expression in LUAD patients was confirmed through Timer2.0 database and tissue microarrays. Immunohistochemical staining for MK2 was performed on LUAD samples to investigate its association with metastasis and invasion. The activity of MK2 was inhibited in LUAD cell lines A549 and H358 using a specific MK2 inhibitor. Subsequently, cell viability, migration, and invasion were assessed. Gene expression changes were confirmed through Western blotting. Additionally, an AKT activator was used to validate the role of the MK2-regulated AKT/MYC signaling pathway.

Results: MK2 expression is significantly higher in LUAD tissues compared to adjacent normal tissues. Reducing MK2 activity not only curtails cell proliferation, migration, and EMT-related invasion in vitro but also disrupts the AKT/MYC signaling axis. Activation of the AKT/MYC pathway can counteract the inhibitory effects of MK2 suppression.

Conclusion: Our findings suggest that MK2 promotes migration and invasion in LUAD through the AKT/MYC signaling pathways, positioning MK2 as a potential therapeutic target in LUAD treatment.

查看原文本刊更多论文

mk2介导的AKT/MYC信号激活促进肺腺癌上皮-间质转化。

目的：蛋白激酶丝裂原活化蛋白激酶活化蛋白激酶2 （MK2）与某些癌症转移和死亡的高风险有关。然而，其在肺腺癌（LUAD）中的确切功能尚不清楚。本研究旨在探讨MK2在LUAD细胞中的功能，并确定其潜在的分子机制。方法：通过Timer2.0数据库和组织芯片检测MK2在LUAD患者中的表达。对LUAD样品进行MK2免疫组化染色，以研究其与转移和侵袭的关系。MK2在LUAD细胞系A549和H358中被特异性的MK2抑制剂抑制。随后，评估细胞活力、迁移和侵袭。Western blotting证实基因表达变化。此外，AKT激活剂被用来验证mk2调控的AKT/MYC信号通路的作用。结果：MK2在LUAD组织中的表达明显高于邻近正常组织。降低MK2活性不仅会抑制细胞增殖、迁移和emt相关的体外侵袭，还会破坏AKT/MYC信号轴。激活AKT/MYC通路可以抵消MK2抑制的抑制作用。结论：我们的研究结果表明，MK2通过AKT/MYC信号通路促进LUAD的迁移和侵袭，将MK2定位为LUAD治疗的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.