m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε-Mediated Activation of WNT and YAP Signaling Pathways

Sep 21, 2026

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Colorectal cancer (CRC) remains poorly understood in terms of the molecular mechanisms that drive progression. This study identifies the m6A-modified RNA reader Proline-rich Coiled-coil 2a (PRRC2A) as markedly upregulated in CRC. Intestinal epithelium-specific deletion of Prrc2a suppresses tumor cell growth, stemness, and migration, whereas PRRC2A overexpression enhances these phenotypes. Multiomics shows PRRC2A directly targets CSNK1E, stabilizing its RNA in an m6A-dependent manner, leading to activation of WNT and YAP signaling. The work further reports transcriptional regulation of PRRC2A by ATF1, highlighting PRRC2A and CK1ε as potential therapeutic targets for CRC.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

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Introduction

Colorectal cancer background

Roles of m6A modifications and m6A reader proteins

WNT/β-catenin signaling in CRC

Hippo/YAP signaling in CRC

RESEARCH ARTICLE [www.advancedscience.com](www.advancedscience.com) m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1􀀂-Mediated Activation ofWNT and YAP Signaling Pathways Xi Wu, Shiyang Wang, Yuwei Pan, Mengzhen Li, Manyu Song, Hanfu Zhang, Min Deng, Xu Yang, Jiuzhi Xu, Shuo Zhang, Jinhua Zhang, Fengchao Wang, Maksim V. Plikus, Cong Lv,* Lu Yu,* and Zhengquan Yu* Colorectal cancer (CRC) is the third most common cancer type and the second highest mortality rate among cancers. However, the mechanisms underlying CRC progression remain to be fully understood. In this work, a recently identiﬁed m6A-modiﬁed RNA reader protein Proline-rich Coiled-coil 2a (PRRC2A) is markedly upregulated in CRC, and intestinal epithelium-speciﬁc deletion of Prrc2a signiﬁcantly suppressed tumor cell growth, stemness, and migratory capacity, while its overexpression promoted these behaviors. Through multiomics analysis, PRRC2A directly targeted CSNK1E (encoding CK1􀀂), maintaining its RNA stability in an m6A-dependent manner, and that elevated CK1􀀂 can concomitantly result in activation ofthe WNT and YAP signaling pathways. Interestingly, PRRC2A is directly regulated by the transcription factor ATF1 in its promoter. In summary, the work reveals a novel mechanism by which m6A reader PRRC2A promotes colorectal cancer progression via CK1􀀂 and aberrant upregulation ofWNT and YAP signaling. Therefore, PRRC2A and CK1􀀂 can be potential therapeutic targets for treating CRC. 1. Introduction Colorectal cancer (CRC) is a common digestive tract tumor with the third highest incidence rate and the second highest mortality rate among cancers, posing a serious threat to human life and health worldwide. [1,2] Understanding the mechanism underlying cancer progression is the foundation for the development of successful strategies for eﬀective cancer prevention and management. N6-methyladenosine (m6A) modiﬁcation is the most prevalent internal modiﬁcation in eukaryotic mRNAs, and its dysregulation plays a critical role in promoting cancer progression. [3–5] m6A modiﬁcations of target RNAs need tobe recognized by m6A reader proteins to regulate RNA export, splicing, translation, and degradation. [3,6] Several m6A reader X. Wu, Z. Yu The First Aﬃliated Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical Sciences Zhengzhou University Zhengzhou, Henan 450052, China E-mail: [zyu@cau.edu.cn](zyu@cau.edu.cn), [zyu@zzu.edu.cn](zyu@zzu.edu.cn) X. Wu, S. Wang, Y. Pan, M. Li, H. Zhang, M. Deng, X. Yang, J. Xu, S. Zhang, L. Yu, Z. Yu State Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193, China E-mail: [yulu@cau.edu.cn](yulu@cau.edu.cn) The ORCID identiﬁcation number(s) for the author(s) of this article can be found under [https://doi.org/10.1002/advs.202406935](https://doi.org/10.1002/advs.202406935)[ ](https://doi.org/10.1002/advs.202406935)© 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. DOI: 10.1002/advs.202406935 M. Song, C. Lv Key Laboratory of Precision Nutrition and Food Quality Ministry of Education Department of Nutrition and Health China Agricultural University Beijing 100193, China E-mail: [lvc@cau.edu.cn](lvc@cau.edu.cn) J. Zhang The college of Life Science and Bioengineering Beijing Jiaotong University Beijing 100044, China F. Wang National Institute of Biological Science Beijing 102206, China M. V. Plikus Department of Developmental and Cell Biology Sue and Bill Gross Stem Cell Research Center Center for Complex Biological Systems University of California Irvine, CA 92697, USA Adv. Sci. 2025, 12, 2406935 2406935 (1 of 20) © 2024 The Author(s) . Advanced Science

FAQs

What role does PRRC2A play in colorectal cancer progression?

PRRC2A is upregulated in colorectal cancer and functionally promotes tumor cell growth, stemness, and migration. Deleting Prrc2a in intestinal epithelium suppresses these cancer phenotypes, while overexpression enhances them.

How does PRRC2A connect to CK1ε and RNA stability?

PRRC2A directly targets CSNK1E, encoding CK1ε, and maintains its RNA stability in an m6A-dependent manner. Increased CK1ε then contributes to downstream activation of WNT and YAP signaling pathways.

What signaling pathways are activated by the PRRC2A–CK1ε axis?

The study links elevated CK1ε to concomitant activation of WNT signaling and YAP signaling pathways. These pathways are described as key drivers of intestinal development and cancer progression.

Sep 21, 2026

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