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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Unraveling the impact of alternative splicing network on cancer immune microenvironment and tumor development: unique

Xiao Zhu1, Mengmeng Zhang2, Qinglan Chen1

  • 1The Second Affiliated Hospital, Guangdong Medical University, Zhanjiang, China.

Computer Methods in Biomechanics and Biomedical Engineering
|December 18, 2025
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Summary

Alternative splicing (AS) generates diverse mRNA leading to cancer. This study identified prognostic AS events and developed signatures, revealing AS

Keywords:
Alternative splicingBayesianMendelian inheritanceimmune microenvironmentnetworkpan-cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Alternative splicing (AS) generates diverse mRNA isoforms.
  • AS plays a critical role in cancer development and progression.

Purpose of the Study:

  • To identify prognostic alternative splicing events across pan-cancer.
  • To construct robust prognostic signatures for cancer patients.
  • To investigate the influence of AS on the tumor immune microenvironment and immunotherapy response.

Main Methods:

  • Utilized Drosophila homologous genes for initial identification.
  • Applied Cox regression analysis to identify prognostic AS events.
  • Validated prognostic signatures using survival and ROC analyses.
  • Analyzed splicing factor regulatory networks and employed Mendelian randomization.

Main Results:

  • Identified significant prognostic AS events across various cancer types.
  • Developed validated prognostic signatures with strong predictive power.
  • Demonstrated that AS significantly impacts the tumor immune microenvironment and immunotherapy outcomes.
  • COL1A1 identified as a key pan-cancer prognostic factor.
  • Revealed genes associated with tumor development through network and MR analyses.

Conclusions:

  • Alternative splicing is a crucial factor in pan-cancer prognosis.
  • AS-derived signatures can serve as valuable prognostic biomarkers.
  • AS influences tumor immunity and response to immunotherapy.
  • Identified COL1A1 and other splicing-related genes as potential therapeutic targets.