Deciphering the role of IGF2BP2 and PRMT5 in gallbladder cancer progression: insights from multi-omics analysis

  • Br J Cancer. 2025 Jun 24. doi: 10.1038/s41416-025-03062-w.
Xinwei Yang  #  1 ,  Lingqi Sun  #  2 ,  Jiamin Guo  3 ,  Yichen Zheng  3 ,  Tonghui Ren  3 ,  Ying Liu  4 ,  Lingnan Zheng  3 ,  Ji Ma  5
Affiliations
  • 1. Department of Biliary Surgery IV, Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai, China.
  • 2. Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 3. Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China.
  • 4. Department of Breast Surgery, The 940 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Lanzhou, PR China.
  • 5. Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China. [email protected].
  • # Contributed equally.
PMID: 40555776 DOI: 10.1038/s41416-025-03062-w
Abstract

Background: Gallbladder Cancer (GBC) is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Elucidating the molecular mechanisms driving GBC progression is essential for identifying novel therapeutic targets.

Methods: Single-cell transcriptomics, high-throughput Sequencing, and proteomics techniques were employed to investigate the role of the IGF2BP2-PRMT5 axis in GBC. Functional assays were conducted to assess cell proliferation, invasion, and migration, while mechanistic studies examined the impact of N6-methyladenosine (m6A) modifications and downstream signalling pathways. Furthermore, a humanised mouse model was utilised to examine the impact of this axis on immune cell infiltration and tumour immune evasion.

Results: IGF2BP2 was found to stabilise PRMT5 expression via m6A modifications, thereby promoting GBC cell proliferation, invasion, and migration. Mechanistically, PRMT5 activated the Akt/mTOR pathway, upregulated SREBP1, and reprogrammed lipid metabolism, leading to increased lipid synthesis and accumulation. Functional assays and in vivo experiments revealed that modulation of the IGF2BP2-PRMT5 axis significantly influenced immune cell infiltration, fostering immune evasion.

Conclusions: The IGF2BP2-PRMT5 axis is critical in GBC progression by orchestrating metabolic reprogramming and immune modulation. Targeting this axis holds potential as a therapeutic strategy for combating GBC.

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