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iMPI: An Integrative Database for MicroProteins Encoded by Intron Retention in Tumors.

Jiamin Hu1, Yongqiang Zheng1, Xin Huang1

  • 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.

Proteomics
|May 11, 2026
PubMed
Summary

Intron retention (IR) can drive cancer, but retained introns may encode novel proteins. Researchers identified and validated thousands of these intron-derived proteins (iORFs) in human cancers, creating a new database, iMPI, for further study.

Keywords:
alternative splicingbiological databasecancercoding potentialintron retention

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Area of Science:

  • Genomics
  • Proteomics
  • Cancer Biology

Background:

  • Aberrant intron retention (IR) is increasingly recognized in cancer pathogenesis and therapeutic resistance.
  • A significant gap exists in understanding the functional role of introns within tumors, particularly their coding potential.
  • Previous research has not comprehensively explored translatable intron ORFs (iORFs) and their encoded proteins in cancer.

Purpose of the Study:

  • To investigate whether retained introns contain undiscovered protein-coding open reading frames (ORFs) capable of encoding proteins.
  • To develop the first comprehensive database resource for microproteins encoded by introns (iMPI).
  • To validate iORFs at the protein level using large-scale proteomic data.

Main Methods:

  • Genome-wide search for translatable intron ORFs (iORFs) in the human GRCh38 genome.
  • Validation of iORFs using proteomic mass spectrometry (MS) data across 27 cancer types.
  • Development of the iMPI database integrating intron information, coding evidence, and protein characteristics.

Main Results:

  • Identified 209,091 introns, with 15,975 strong candidates for coding potential.
  • Validated 5,823 iORFs within 4,751 introns across 27 cancer types via MS data.
  • Established iMPI, a user-friendly web resource detailing iORF-encoded microproteins, their locations, and structures.

Conclusions:

  • Retained introns represent a significant source of novel protein-coding regions (iORFs) in human cancers.
  • The iMPI database provides a valuable resource for exploring the role of iORF-encoded microproteins in cancer.
  • This research expands our understanding of gene regulation and protein diversity in the context of cancer.