A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis
Abstract Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin...
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Nature Publishing Group
2024-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-07248-7 |
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| author | Zeyi Guo Zhongzhe Li Jinhao Guo Luxiang Gan Haiyu Mo Jiajun Zhang Yu Fu Yi Wang Meixian Jin Yanping Wu Qingyu Xie Kunjiang Tan Chunming Wang Yuyan Xu Guolin He Lei Cai Yi Gao Mingxin Pan Shunjun Fu |
| author_facet | Zeyi Guo Zhongzhe Li Jinhao Guo Luxiang Gan Haiyu Mo Jiajun Zhang Yu Fu Yi Wang Meixian Jin Yanping Wu Qingyu Xie Kunjiang Tan Chunming Wang Yuyan Xu Guolin He Lei Cai Yi Gao Mingxin Pan Shunjun Fu |
| author_sort | Zeyi Guo |
| collection | DOAJ |
| description | Abstract Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin promoted HCC progression by regulating the AKT signaling pathway. To investigate the upstream regulatory mechanism, the results from RNA Immunoprecipitation and RNA pull-down indicated that the specific region of circIPP2A2 interacted with Hornerin. Additionally, patients with circIPP2A2 upregulation exhibited a poorer survival outcome following surgery compared to the cases with downregulated circIPP2A2. After the structure verification of circIPP2A2, loss-of-function studies using a lentiviral vector revealed that circIPP2A2 downregulation significantly inhibited HCC tumorigenesis and progression both in vitro and in vivo. Mechanistically, the m7G-MeRIP results demonstrated significant enrichment of circIPP2A2. Subsequent studies validated that METTL1 influenced the stability of circIPP2A2 and its binding affinity with Hornerin. Immunoprecipitation and immunofluorescence indicated that circIPP2A2 served as a molecular scaffold to facilitate Hornerin to interact with PI3K. In conclusion, our findings reveal that circIPP2A2, regulated by N7-methylguanosine modification, promotes malignant behaviors in HCC by serving as a molecular scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis. Targeting circIPP2A2 may be a promising therapeutic strategy for patients with HCC. |
| format | Article |
| id | doaj-art-41249c2d90e24830a74c2b1dd6f4625d |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
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| series | Cell Death and Disease |
| spelling | doaj-art-41249c2d90e24830a74c2b1dd6f4625d2025-08-20T02:38:35ZengNature Publishing GroupCell Death and Disease2041-48892024-11-01151111410.1038/s41419-024-07248-7A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axisZeyi Guo0Zhongzhe Li1Jinhao Guo2Luxiang Gan3Haiyu Mo4Jiajun Zhang5Yu Fu6Yi Wang7Meixian Jin8Yanping Wu9Qingyu Xie10Kunjiang Tan11Chunming Wang12Yuyan Xu13Guolin He14Lei Cai15Yi Gao16Mingxin Pan17Shunjun Fu18Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityShanxi Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityDepartment of Anesthesiology of the Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityThe Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityDepartment of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical UniversityAbstract Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin promoted HCC progression by regulating the AKT signaling pathway. To investigate the upstream regulatory mechanism, the results from RNA Immunoprecipitation and RNA pull-down indicated that the specific region of circIPP2A2 interacted with Hornerin. Additionally, patients with circIPP2A2 upregulation exhibited a poorer survival outcome following surgery compared to the cases with downregulated circIPP2A2. After the structure verification of circIPP2A2, loss-of-function studies using a lentiviral vector revealed that circIPP2A2 downregulation significantly inhibited HCC tumorigenesis and progression both in vitro and in vivo. Mechanistically, the m7G-MeRIP results demonstrated significant enrichment of circIPP2A2. Subsequent studies validated that METTL1 influenced the stability of circIPP2A2 and its binding affinity with Hornerin. Immunoprecipitation and immunofluorescence indicated that circIPP2A2 served as a molecular scaffold to facilitate Hornerin to interact with PI3K. In conclusion, our findings reveal that circIPP2A2, regulated by N7-methylguanosine modification, promotes malignant behaviors in HCC by serving as a molecular scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis. Targeting circIPP2A2 may be a promising therapeutic strategy for patients with HCC.https://doi.org/10.1038/s41419-024-07248-7 |
| spellingShingle | Zeyi Guo Zhongzhe Li Jinhao Guo Luxiang Gan Haiyu Mo Jiajun Zhang Yu Fu Yi Wang Meixian Jin Yanping Wu Qingyu Xie Kunjiang Tan Chunming Wang Yuyan Xu Guolin He Lei Cai Yi Gao Mingxin Pan Shunjun Fu A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis Cell Death and Disease |
| title | A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis |
| title_full | A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis |
| title_fullStr | A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis |
| title_full_unstemmed | A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis |
| title_short | A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis |
| title_sort | n7 methylguanosine modified circular rna circipp2a2 promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the hornerin pi3k akt gsk3β axis |
| url | https://doi.org/10.1038/s41419-024-07248-7 |
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