Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers

Ka-Yun Ban1, Yong-Woo Na2, Juhan Song1

  • 1Department of Health Science and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHST, Incheon, 21999, Republic of Korea.

Scientific Reports
|November 7, 2024
PubMed

Insights

Oncogenic KRAS mutations alter RNA-binding protein (RBP) networks. This study identified 35 cancer-associated RBPs, revealing new therapeutic targets for KRAS-mutant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • KRAS is a frequently mutated oncogene in cancer, driving significant alterations in cellular signaling and gene expression.
  • RNA-binding proteins (RBPs) are crucial regulators of post-transcriptional gene expression, and their dysregulation is common in cancer.
  • The impact of oncogenic KRAS mutations on RBP-mediated post-transcriptional networks is not well understood.

Purpose of the Study:

  • To systematically investigate how oncogenic KRAS mutations affect RNA-binding protein networks.
  • To identify specific RBPs and their altered RNA-binding activities in KRAS-mutant cancers.
  • To provide a resource for understanding RBP regulation in KRAS-driven malignancies and inform therapeutic strategies.

Main Methods:

  • Systematic analysis of RNA-binding protein networks in the context of oncogenic KRAS activation.
  • Identification and characterization of RBPs exhibiting altered RNA binding in KRAS-mutant cancer cells.
  • Functional validation of key RBPs, such as PDCD11 and ELAVL2, in KRAS-mutant cancer models.

Main Results:

  • Identified 35 cancer-associated RBPs with altered RNA binding in response to oncogenic KRAS.
  • Discovered PDCD11 as essential for the viability of KRAS-mutant cancers.
  • Found ELAVL2 regulates cell migration in KRAS-mutant lung cancers.

Conclusions:

  • Oncogenic KRAS mutations significantly reshape the RNA-binding protein regulatory landscape.
  • Specific RBPs like PDCD11 and ELAVL2 are critical players in KRAS-mutant cancer progression.
  • This research offers a valuable resource and potential therapeutic targets for KRAS-mutant cancers.

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