TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation

Sep 24, 2026

Uploaded by James

The transcription factor PBX1 functions as an oncogene in multiple cancers, while its contribution to non-small cell lung cancer (NSCLC) and the underlying mechanism remain unclear. PBX1 is downregulated in NSCLC tissues and suppresses NSCLC cell proliferation and migration. TRIM26 is identified in PBX1 immunoprecipitates and ubiquitinates PBX1 through K48-linked polyubiquitination, leading to proteasomal degradation. TRIM26 activity requires its C-terminal RING domain, enhances proliferation and predicts poor prognosis, promoting xenograft growth. TRIM26 is proposed as a novel therapeutic target.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Introduction

Materials and Methods

Primary NSCLC tissues

Ivyspring International Publisher InternationalJournal of Biological Sciences 2023; 19(9): 2803-2816. doi: 10.7150/ijbs.81726 Research Paper TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation Yuening Sun1,2\#, Peng Lin3\#, Xiumin Zhou4\#, Ying Ren3, Yuanming He1, Jingpei Liang1, Zhigang Zhu6, Xiaofeng Xu7􀀍, Xinliang Mao1,2,5􀀍 1. Guangdong Institute of Cardiovascular Diseases, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511436, P. R. China. 2. Guangdong Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, P. R. China. 3. Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, P. R. China. 4. Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China. 5. Department of Biology, GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation, Guangzhou Medical University, 511436, P. R. China. 6. Division of Hematology & Oncology, Department of Geriatrics, Guangzhou First People's Hospital, College of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P. R. China. 7. Department of Urology, Jinling Hospital of Nanjing University, Nanjing, 210093, P. R. China \# These authors contributed equally to this study. 􀀍 Corresponding authors: Dr. Xinliang Mao ([xinliangmao@gzhmu.edu.cn](xinliangmao@gzhmu.edu.cn)), Guangdong Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University. or Dr. Xiaofeng Xu ([shxxf@sina.com](shxxf@sina.com)), Department of Oncology, Jinling Hospital of Nanjing University, Nanjing, China. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions. Received: 2022.12.10; Accepted: 2023.05.21; Published: 2023.05.29 Abstract The transcription factor PBX1 is regarded as an oncogene in various cancers, but its role in non-small cell lung cancer (NSCLC) and the detailed mechanism is not known. In the present study, we found that PBX1 is downregulated in NSCLC tissues and inhibits NSCLC cell proliferation and migration. Subsequently, we performed an affinity purification-coupled tandem mass spectrometry (MS/MS) and found the ubiquitin ligase TRIM26 in the PBX1 immunoprecipitates. Moreover, TRIM26 binds to and mediates PBX1 for K48-linked polyubiquitination and proteasomal degradation. Noticeably, TRIM26 activity depends on its C-terminal RING domain when it is deleted TRIM26 loses its function towards PBX1. TRIM26 further inhibits PBX1 transcriptional activity and downregulates the PBX1 downstream genes, such as RNF6. Moreover, we found that overexpression of TRIM26 significantly promotes NSCLC proliferation, colony formation, and migration in contradiction to PBX1. TRIM26 is highly expressed in NSCLC tissues and predicts poor prognosis. Lastly, the growth NSCLC xenografts is promoted by overexpression of TRIM26 but is suppressed by TRIM26 knockout. In conclusion, TRIM26 is a ubiquitin ligase of PBX1 and it promotes while PBX1 inhibits NSCLC tumor growth. TRIM26 might be a novel therapeutic target for the treatment of NSCLC. Keywords: Non-small cell lung cancer; Pre-B cell leukemia transcription factor 1; Tripartite motif containing 26 Introduction Lung cancer is the most frequent cause of cancer-related deaths worldwide, accounting for an estimated 1.6 million deaths a year, 85% of which are non-small cell lung cancers1. NSCLC is a molecularly heterogeneous disease and understanding its biology is crucial for the development

FAQs

What is PBX1’s role in non-small cell lung cancer (NSCLC)?

PBX1 is downregulated in NSCLC tissues and inhibits NSCLC cell proliferation and migration.

How was TRIM26 identified as related to PBX1?

Affinity purification coupled with tandem mass spectrometry found the ubiquitin ligase TRIM26 in PBX1 immunoprecipitates.

What effect does TRIM26 have on PBX1 and NSCLC progression?

TRIM26 binds PBX1, mediates K48-linked polyubiquitination and proteasomal degradation, and promotes NSCLC proliferation, migration, and xenograft growth.

Sep 24, 2026

Uploaded by James