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Published on: July 17, 2019
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.
Abstract:
KRAS is one of the most frequently mutated oncogenes across various cancers. Oncogenic KRAS mutations rewire cellular signaling, leading to significant alterations in gene expression. RNA-binding proteins (RBPs) play a pivotal role in gene expression regulation by post-transcriptionally controlling various aspects of RNA metabolism. It has become clear that interactions between RBPs and RNA are frequently dysregulated in numerous cancers. However, how oncogenic KRAS mutations reshape the post-transcriptional regulatory network mediated by RBPs remains poorly understood. In this study, we systematically dissected oncogenic KRAS-driven alterations of RNA-RBP networks. We identified 35 cancer-associated RBPs with either increased or decreased RNA binding upon oncogenic KRAS activation, including PDCD11, which is essential for the viability of KRAS mutant cancers, and ELAVL2, which regulates cell migration in KRAS mutant lung cancers. Our study serves as a crucial resource for elucidating RBP regulatory networks in KRAS mutant cancers and may provide new avenues for therapeutic strategies targeting KRAS mutant malignancies.
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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