TBRG4 as a prognostic biomarker and key regulator of cell cycle and EMT in lung cancer

Ansheng Wang; Qiao Ge; Zhenkai Fan; Bing Xia; Zhao Jin; Haitao Liu; Haiwei Sang; Qicai Li; Congli Zhang; Haonan Zhu

doi:10.17305/bb.2025.11353

Authors

Ansheng Wang Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0000-0002-8318-4786
Qiao Ge Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0009-0009-3530-0269
Zhenkai Fan Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0009-0002-7828-5205
Bing Xia Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0009-0008-9806-7938
Zhao Jin Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0009-0001-4477-4898
Haitao Liu Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0000-0002-7008-2633
Haiwei Sang Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0000-0003-1462-9996
Qicai Li Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0009-0004-7327-9062
Congli Zhang Department of Anesthesia, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China https://orcid.org/0000-0002-0263-1434
Haonan Zhu Department of Thoracic Surgery, Fuyang People’s Hospital, Fuyang, Anhui, China https://orcid.org/0009-0007-7786-4957

DOI:

https://doi.org/10.17305/bb.2025.11353

Keywords:

Lung cancer, TBRG4, cell cycle, epithelial-mesenchymal transition, prognostic biomarker

Abstract

Transforming growth factor β regulator 4 (TBRG4) is upregulated in lung cancer, but its biological role and underlying mechanisms remain poorly understood. In this study, we analyzed pancancer gene expression profiles and clinical data from University of California, Santa Cruz Xena (UCSC Xena) to evaluate the prognostic significance of TBRG4 using univariate and multivariate Cox regression analyses. Genes with a Pearson correlation coefficient above 0.4 with TBRG4 in lung cancer were identified via UALCAN, followed by pathway enrichment analyses to explore their functional associations. To investigate TBRG4’s role in lung cancer progression, we assessed cell proliferation, colony formation, and cell cycle alterations in lung cancer cells following TBRG4 knockdown. Western blot analysis was performed to examine the effects of TBRG4 depletion on key cell cycle regulators and epithelial-mesenchymal transition (EMT) markers. Additionally, the biological significance of TBRG4 was evaluated in vivo using a mouse xenograft model. TBRG4 knockdown significantly inhibited cell proliferation and colony formation while inducing cell cycle arrest and apoptosis in lung cancer cells. Analysis of co-expressed genes in the The Cancer Genome Atlas - Lung Adenocarcinoma (TCGA-LUAD) cohort revealed enrichment in cell cycle-related pathways, aligning with our experimental findings. Furthermore, TBRG4 depletion reduced EMT marker expression and suppressed tumor growth in vivo. Collectively, these findings suggest that TBRG4 may serve as a promising prognostic biomarker and therapeutic target in lung cancer.