DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment

Abstract LUAD, a prevalent lung cancer with high mortality, has seen increased focus on molecular targeted therapies due to patient heterogeneity. Among these prospects, dystrophin-associated protein 2 (DRP2), a critical component of the dystrophin complex, underpins membrane-associated structures v...

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Main Authors: Zhimeng Chen, Hao Shi, Wenxuan Hu, Jian Yang, Yuxuan Xing, Xin Lv, Chenzhuo Wu, Cheng Ding, Jun Zhao
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-01611-0
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author Zhimeng Chen
Hao Shi
Wenxuan Hu
Jian Yang
Yuxuan Xing
Xin Lv
Chenzhuo Wu
Cheng Ding
Jun Zhao
author_facet Zhimeng Chen
Hao Shi
Wenxuan Hu
Jian Yang
Yuxuan Xing
Xin Lv
Chenzhuo Wu
Cheng Ding
Jun Zhao
author_sort Zhimeng Chen
collection DOAJ
description Abstract LUAD, a prevalent lung cancer with high mortality, has seen increased focus on molecular targeted therapies due to patient heterogeneity. Among these prospects, dystrophin-associated protein 2 (DRP2), a critical component of the dystrophin complex, underpins membrane-associated structures vital for intercellular interactions in vertebrates. Aberrations in DRP2 function have been linked to the occurrence and development of multiple diseases, prompting an inquiry into its potential link with LUAD progression. To delve into the potential roles of DRP2 in LUAD, we initiated a comprehensive investigation. First, we analyzed DRP2 expression patterns in LUAD using bioinformatics tools. This was subsequently validated through immunohistochemical staining, quantitative PCR, and Western blot analyses. Furthermore, we assessed the functional implications of DRP2 in LUAD cells, both in vitro and in vivo, utilizing assays such as cell cycle analysis, CCK-8 proliferation assay, Colony formation assay EdU incorporation, Transwell migration test, scratch wound healing assay, flow cytometry, and mouse models for tumor xenograft and metastasis. Results showed a strong correlation between high DRP2 expression in LUAD and poorer survival. Notably, DRP2 knockdown accelerated LUAD progression via the EMT pathway. These findings highlight DRP2’s crucial role in LUAD and its potential as a therapeutic target.
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spelling doaj-art-df06b3c151de4ab4a159a8ddd4c0324a2025-08-20T03:10:13ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-01611-0DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatmentZhimeng Chen0Hao Shi1Wenxuan Hu2Jian Yang3Yuxuan Xing4Xin Lv5Chenzhuo Wu6Cheng Ding7Jun Zhao8Department of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityLaboratory of Cancer Molecular Genetics, Soochow University, Medical College of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversityAbstract LUAD, a prevalent lung cancer with high mortality, has seen increased focus on molecular targeted therapies due to patient heterogeneity. Among these prospects, dystrophin-associated protein 2 (DRP2), a critical component of the dystrophin complex, underpins membrane-associated structures vital for intercellular interactions in vertebrates. Aberrations in DRP2 function have been linked to the occurrence and development of multiple diseases, prompting an inquiry into its potential link with LUAD progression. To delve into the potential roles of DRP2 in LUAD, we initiated a comprehensive investigation. First, we analyzed DRP2 expression patterns in LUAD using bioinformatics tools. This was subsequently validated through immunohistochemical staining, quantitative PCR, and Western blot analyses. Furthermore, we assessed the functional implications of DRP2 in LUAD cells, both in vitro and in vivo, utilizing assays such as cell cycle analysis, CCK-8 proliferation assay, Colony formation assay EdU incorporation, Transwell migration test, scratch wound healing assay, flow cytometry, and mouse models for tumor xenograft and metastasis. Results showed a strong correlation between high DRP2 expression in LUAD and poorer survival. Notably, DRP2 knockdown accelerated LUAD progression via the EMT pathway. These findings highlight DRP2’s crucial role in LUAD and its potential as a therapeutic target.https://doi.org/10.1038/s41598-025-01611-0DRP2Lung adenocarcinomaEMTCell cycleInvasionMigration
spellingShingle Zhimeng Chen
Hao Shi
Wenxuan Hu
Jian Yang
Yuxuan Xing
Xin Lv
Chenzhuo Wu
Cheng Ding
Jun Zhao
DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment
Scientific Reports
DRP2
Lung adenocarcinoma
EMT
Cell cycle
Invasion
Migration
title DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment
title_full DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment
title_fullStr DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment
title_full_unstemmed DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment
title_short DRP2 promotes EMT and serves as a potential therapeutic target for LUAD treatment
title_sort drp2 promotes emt and serves as a potential therapeutic target for luad treatment
topic DRP2
Lung adenocarcinoma
EMT
Cell cycle
Invasion
Migration
url https://doi.org/10.1038/s41598-025-01611-0
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