TRIM28‐Derived Peptide Exerts Anti‐Tumor Roles by Stabilizing Tumor Suppressive BRD7 Protein in Multiple Cancers
5 affiliations
- 1NHC Key Laboratory of Carcinogenesis Hunan Key Laboratory of Oncotarget Gene Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China
- 2Cancer Research Institute and School of Basic Medical Sciences Central South University Changsha China
- 3The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Central South University Changsha China
- 4Xiangya School of Medicine Central South University Changsha China
- 5Department of Blood Transfusion The Third Xiangya Hospital Central South University Changsha Hunan China
Abstract
BRD7 serves as a critical tumor suppressor, yet it is frequently inactivated via ubiquitination‐mediated proteasomal degradation, facilitating tumor progression and metastasis. Although stabilizing or activating BRD7 represents a promising therapeutic strategy, pharmacological agents to achieve this remain limited. Here, we aimed to develop a peptide‐based approach to enhance BRD7 protein stability. We first mapped the TRIM28‐BRD7 interaction to the 299–349 aa region within the Coiled‐coil domain of TRIM28. Based on this interface, we designed two α‐helical peptides, TAB12 and TAB14, that mimic the key structural features. Mechanistically, TAB12 exhibits strong binding affinity toward BRD7 protein and competitively disrupts the TRIM28‐BRD7 interaction, thereby blocking TRIM28‐mediated BRD7 ubiquitination and stabilizing endogenous BRD7. In vitro functional assays demonstrated that TAB12 markedly inhibits tumor cell proliferation, migration, and invasion, induces cell apoptosis, and presents low cytotoxicity toward normal cells. Subsequent rescue experiments confirmed that BRD7 knockdown substantially abrogates the anti‐tumor effects of TAB12, verifying that TAB12's function depends on stabilizing BRD7. Furthermore, in vivo animal models validated that TAB12 significantly suppresses tumor growth with a favorable safety profile. Therefore, this study identifies a novel peptide agent that exerts broad anti‐tumor effects by stabilizing BRD7, offering a feasible strategy for restoring tumor suppressor function.
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BibTeX
@article{wei2026trim28derived,
title = {{TRIM28‐Derived Peptide Exerts Anti‐Tumor Roles by Stabilizing Tumor Suppressive BRD7 Protein in Multiple Cancers}},
author = {Qingqing Wei and Changning Xue and Mengna Li and Jianxia Wei and Lemei Zheng and Shipeng Chen and Yijie Wang and Yumei Duan and Yanwei Luo and Wei Xiong and Ming Zhou},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.76974},
url = {https://doi.org/10.1002/advs.76974},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TRIM28‐Derived Peptide Exerts Anti‐Tumor Roles by Stabilizing Tumor Suppressive BRD7 Protein in Multiple Cancers
AU - Qingqing Wei
AU - Changning Xue
AU - Mengna Li
AU - Jianxia Wei
AU - Lemei Zheng
AU - Shipeng Chen
AU - Yijie Wang
AU - Yumei Duan
AU - Yanwei Luo
AU - Wei Xiong
AU - Ming Zhou
PY - 2026
DA - 2026/08/05
JO - Advanced Science
DO - 10.1002/advs.76974
UR - https://doi.org/10.1002/advs.76974
AB - BRD7 serves as a critical tumor suppressor, yet it is frequently inactivated via ubiquitination‐mediated proteasomal degradation, facilitating tumor progression and metastasis. Although stabilizing or activating BRD7 represents a promising therapeutic strategy, pharmacological agents to achieve this remain limited. Here, we aimed to develop a peptide‐based approach to enhance BRD7 protein stability. We first mapped the TRIM28‐BRD7 interaction to the 299–349 aa region within the Coiled‐coil domain of TRIM28. Based on this interface, we designed two α‐helical peptides, TAB12 and TAB14, that mimic the key structural features. Mechanistically, TAB12 exhibits strong binding affinity toward BRD7 protein and competitively disrupts the TRIM28‐BRD7 interaction, thereby blocking TRIM28‐mediated BRD7 ubiquitination and stabilizing endogenous BRD7. In vitro functional assays demonstrated that TAB12 markedly inhibits tumor cell proliferation, migration, and invasion, induces cell apoptosis, and presents low cytotoxicity toward normal cells. Subsequent rescue experiments confirmed that BRD7 knockdown substantially abrogates the anti‐tumor effects of TAB12, verifying that TAB12's function depends on stabilizing BRD7. Furthermore, in vivo animal models validated that TAB12 significantly suppresses tumor growth with a favorable safety profile. Therefore, this study identifies a novel peptide agent that exerts broad anti‐tumor effects by stabilizing BRD7, offering a feasible strategy for restoring tumor suppressor function.
SN - 2198-3844
ER -