m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways
Source abstract
Abstract
Abstract 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 CK1ε), maintaining its RNA stability in an m6A‐dependent manner, and that elevated CK1ε can concomitantly result in activation of the 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 CK1ε and aberrant upregulation of WNT and YAP signaling. Therefore, PRRC2A and CK1ε can be potential therapeutic targets for treating CRC.
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Research context
OpenAlex topics: RNA modifications and cancer · RNA Research and Splicing · Cancer-related molecular mechanisms research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
The First Affiliated Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical Sciences Zhengzhou University Zhengzhou Henan 450052 China
State Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 China
Key Laboratory of Precision Nutrition and Food Quality Ministry of Education Department of Nutrition and Health China Agricultural University Beijing 100193 China
The college of Life Science and Bioengineering Beijing Jiaotong University Beijing 100044 China
National Institute of Biological Science Beijing 102206 China
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
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China
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