2. Academic Validation
  3. Multi-omics analysis and preliminary experimental validation of acetyl tributyl citrate (ATBC) promoting bladder cancer progression via the AKR1B1/EMT axis

Multi-omics analysis and preliminary experimental validation of acetyl tributyl citrate (ATBC) promoting bladder cancer progression via the AKR1B1/EMT axis

  • Environ Pollut. 2026 May 15:397:127970. doi: 10.1016/j.envpol.2026.127970.
Jirong Jie 1,  Qiong Wang 2,  Zhifeng Chen 3,  Chenxi Hu 4,  Zhuocheng Lai 5,  Sulun Ke 6,  Yuanchao Zhu 7,  Fei Li 8,  Qin Fan 9,  Wanlong Tan 10
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China; Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 2 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 3 Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 4 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 5 Department of Urology, Nanhai District People's Hospital of Foshan, Foshan, 528200, Guangdong Province, China. Electronic address: [email protected].
  • 6 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 7 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 8 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 9 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 10 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
PMID: 41846032 DOI: 10.1016/j.envpol.2026.127970
Abstract

Acetyl Tributyl Citrate (ATBC) is a widely used plasticizer that has been increasingly linked to Cancer risks. However, its toxicological impact on bladder Cancer (BCa) remains unclear. This study aimed to systematically investigate the molecular targets and mechanisms of ATBC in BCa using integrated computational and experimental approaches. The oncogenic effects of ATBC were assessed via plate colony formation and transwell migration assays. Potential protein targets of ATBC were predicted by integrating the Pharmmapper, SwissTargetPrediction, and TargetNet databases. Functional enrichment analyses were conducted to identify relevant signaling pathways. Molecular docking and dynamics simulations were utilized to validate the interaction between ATBC and the key target AKR1B1. The R package "scTenifoldKnk" was employed for in silico knockout analysis. In vivo experiments and Western blot analysis confirmed that ATBC regulates epithelial-mesenchymal transition (EMT) through AKR1B1. Functional experiments showed that ATBC promoted BCa cell proliferation and migration. A total of 461 potential ATBC binding targets were identified, of which 142 were associated with BCa based on differential expression analysis. Prognostic modeling prioritized twelve key genes and AKR1B1 exhibited the strongest binding affinity to ATBC. Molecular dynamics simulations confirmed the stability of the ATBC-AKR1B1 complex. Multi-omics analyses revealed that AKR1B1 was significantly upregulated in BCa and correlated with advanced disease stage and poor prognosis. In silico knockout analysis revealed the relationship between AKR1B1 and EMT. Western blot and transwell migration assays revealed that ATBC promoted EMT and migration of BCa cells, whereas knockdown of AKR1B1 inhibited this effect. Our study elucidates the role of ATBC in promoting BCa progression and identifies AKR1B1 as a key functional target. These findings provid crucial insights into the environmental toxicology of plasticizers and establish a theoretical foundation for future preventive and therapeutic strategies against ATBC-related malignancies.

Keywords

AKR1B1; Acetyl tributyl citrate; Bladder cancer; Molecular docking.

Figures
Products