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

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 con...

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Main Authors: Ka-Yun Ban, Yong-woo Na, Juhan Song, Jong-Seo Kim, Jimi Kim
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-78333-2
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author Ka-Yun Ban
Yong-woo Na
Juhan Song
Jong-Seo Kim
Jimi Kim
author_facet Ka-Yun Ban
Yong-woo Na
Juhan Song
Jong-Seo Kim
Jimi Kim
author_sort Ka-Yun Ban
collection DOAJ
description 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.
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spelling doaj-art-aac83e4b03e942519bbde17cac7fb2192025-08-20T02:50:07ZengNature PortfolioScientific Reports2045-23222024-11-0114111010.1038/s41598-024-78333-2Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancersKa-Yun Ban0Yong-woo Na1Juhan Song2Jong-Seo Kim3Jimi Kim4Department of Health Science and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHSTSchool of Biological Sciences, Seoul National UniversityDepartment of Health Science and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHSTSchool of Biological Sciences, Seoul National UniversityDepartment of Health Science and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHSTAbstract 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.https://doi.org/10.1038/s41598-024-78333-2
spellingShingle Ka-Yun Ban
Yong-woo Na
Juhan Song
Jong-Seo Kim
Jimi Kim
Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers
Scientific Reports
title Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers
title_full Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers
title_fullStr Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers
title_full_unstemmed Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers
title_short Protein-RNA interaction dynamics reveal key regulators of oncogenic KRAS-driven cancers
title_sort protein rna interaction dynamics reveal key regulators of oncogenic kras driven cancers
url https://doi.org/10.1038/s41598-024-78333-2
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