Related Experiment Video

Updated: Jan 9, 2026

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
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Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

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Alternative splicing of KRAS exon 4 promotes tumor progression via enhanced KRAS4A oncogenic activity

Namjoon Cho1, Eunhye Kwon1, Si-Eon Kim1

  • 1Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea.

Animal Cells and Systems
|December 10, 2025
PubMed

Insights

This study reveals that KRAS4A, a KRAS splicing variant, enhances oncogenic properties in cancer. Key regulators RBM47 and PTBP1 promote KRAS alternative splicing, offering new therapeutic targets for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • KRAS is a known oncogene with frequent mutations in human cancers.
  • The functional roles of KRAS splicing isoforms, particularly those involving exon 4 alternative splicing, are not well understood.
  • Understanding these isoforms is crucial for comprehending KRAS-driven tumorigenesis.

Purpose of the Study:

  • To investigate the expression patterns and functional significance of KRAS exon 4 splicing variants in human cancers.
  • To identify regulatory factors involved in KRAS alternative splicing.
  • To explore the therapeutic potential of targeting KRAS alternative splicing.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) data to examine KRAS splicing variant expression in cancer tissues.
  • Functional assays to compare the oncogenic properties of KRAS4A and KRAS4B.
  • Identification of regulatory proteins (RBM47, PTBP1) influencing KRAS exon 4 inclusion.

Main Results:

  • Specific cancer types show higher expression of the E4-included KRAS4A variant compared to the E4-excluded KRAS4B variant.
  • KRAS4A exhibits significantly enhanced oncogenic properties compared to KRAS4B.
  • RBM47 and PTBP1 were identified as key regulators promoting KRAS exon 4 inclusion.

Conclusions:

  • KRAS alternative splicing, specifically exon 4 inclusion leading to KRAS4A, contributes to enhanced tumor progression.
  • RBM47 and PTBP1 play critical roles in mediating this oncogenic splicing event.
  • Targeting KRAS alternative splicing presents a promising therapeutic strategy for cancer treatment.
Keywords:
KRASalternative splicingcancer progressiononcogenesplicing factors

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