m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways
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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406935 |
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| author | 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 Zhengquan Yu |
| author_facet | 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 Zhengquan Yu |
| author_sort | Xi Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cfa038814d0a4b14bd7a81fcf0f10809 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-cfa038814d0a4b14bd7a81fcf0f108092025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202406935m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling PathwaysXi Wu0Shiyang Wang1Yuwei Pan2Mengzhen Li3Manyu Song4Hanfu Zhang5Min Deng6Xu Yang7Jiuzhi Xu8Shuo Zhang9Jinhua Zhang10Fengchao Wang11Maksim V. Plikus12Cong Lv13Lu Yu14Zhengquan Yu15The First Affiliated Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical Sciences Zhengzhou University Zhengzhou Henan 450052 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaKey Laboratory of Precision Nutrition and Food Quality Ministry of Education Department of Nutrition and Health China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaThe college of Life Science and Bioengineering Beijing Jiaotong University Beijing 100044 ChinaNational Institute of Biological Science Beijing 102206 ChinaDepartment of Developmental and Cell Biology Sue and Bill Gross Stem Cell Research Center Center for Complex Biological Systems University of California Irvine CA 92697 USAKey Laboratory of Precision Nutrition and Food Quality Ministry of Education Department of Nutrition and Health China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaThe First Affiliated Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical Sciences Zhengzhou University Zhengzhou Henan 450052 ChinaAbstract 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.https://doi.org/10.1002/advs.202406935ATF1CK1εcolorectal cancerHippo/YAP pathwayPRRC2AWNT pathway |
| spellingShingle | 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 Zhengquan Yu m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways Advanced Science ATF1 CK1ε colorectal cancer Hippo/YAP pathway PRRC2A WNT pathway |
| title | m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways |
| title_full | m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways |
| title_fullStr | m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways |
| title_full_unstemmed | m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways |
| title_short | m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways |
| title_sort | m6a reader prrc2a promotes colorectal cancer progression via ck1ε mediated activation of wnt and yap signaling pathways |
| topic | ATF1 CK1ε colorectal cancer Hippo/YAP pathway PRRC2A WNT pathway |
| url | https://doi.org/10.1002/advs.202406935 |
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