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Background <p>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.</p> Methods <p>Single-cell transcriptomics, high-throughput sequencing, and proteomics techniques were employed to investigate the role of the <i>IGF2BP2</i>-<i>PRMT5</i> 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.</p> Results <p><i>IGF2BP2</i> was found to stabilise <i>PRMT5</i> expression via m6A modifications, thereby promoting GBC cell proliferation, invasion, and migration. Mechanistically, <i>PRMT5</i> activated the AKT/mTOR pathway, upregulated <i>SREBP1</i>, and reprogrammed lipid metabolism, leading to increased lipid synthesis and accumulation. Functional assays and in vivo experiments revealed that modulation of the <i>IGF2BP2</i>-<i>PRMT5</i> axis significantly influenced immune cell infiltration, fostering immune evasion.</p> Conclusions <p>The <i>IGF2BP2</i>-<i>PRMT5</i> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年6月24日

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  • Xinwei Yang,
  • Lingqi Sun,
  • Jiamin Guo,
  • Yichen Zheng,
  • Tonghui Ren,
  • Ying Liu,
  • Lingnan Zheng,
  • Ji Ma

摘要

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.