Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma
Abstract Background The insulin-like growth factor 2 (IGF2) and H19 are overexpressed in hepatocellular carcinoma (HCC). IGF2-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in IGF2 and H19 overexpression regulation and its role in...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-024-02204-7 |
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| author | Weiwei Chen Chutian Wu Yuting Li Tonghua Wang Miaoling Huang Min Wang Linjing Long Yanfang Chen Shufen Feng Xuyou Liu Shaohui Tang |
| author_facet | Weiwei Chen Chutian Wu Yuting Li Tonghua Wang Miaoling Huang Min Wang Linjing Long Yanfang Chen Shufen Feng Xuyou Liu Shaohui Tang |
| author_sort | Weiwei Chen |
| collection | DOAJ |
| description | Abstract Background The insulin-like growth factor 2 (IGF2) and H19 are overexpressed in hepatocellular carcinoma (HCC). IGF2-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in IGF2 and H19 overexpression regulation and its role in HCC. Methods Firstly, the effect of miR-483-5p on the expression of IGF2 and H19, and the binding of miR-483-5p to IGF2/H19 enhancer were evaluated in HCC cells. Next, miR-483-5p-mediated IGF2/H19 enhancer activation and its mechanism were investigated in HCC cells. Then, the mechanism by which active IGF2/H19 enhancer mediated by miR-483-5p activate IGF2/H19 promoters was studied in HCC cells. Finally, the effect of MED1 on the expression of IGF2/H19 as well as the malignant phenotype of HCC cells in vitro and in vivo mediated by miR-483-5p was evaluated. Results Mir-483-5p up-regulated IGF2 P2 mRNA-P4 mRNA and H19 expression by binding to IGF2/H19 enhancer resulting in IGF2/H19 enhancer activation in HCC cells. Mechanistically, miR-483-5p increased recruitment of Ago1 and Ago2 at IGF2/H19 enhancer and then activated transcription of IGF2/H19 eRNA by RNA polymerase II and p300, which further induced chromatin loops formation between IGF2/H19 enhancer and IGF2/H19 promoters to activate IGF2/H19 promoters via IGF2/H19 eRNA-MED1-IGF2/H19 promoters complex in HCC cells. In this process, MED1 promoted chromatin loops formation as well as the malignant phenotype of HCC cells in vitro and in vivo mediated by miR-483-5p. Conclusions miR-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via DNA loops, thereby promoting the malignant progression of HCC. |
| format | Article |
| id | doaj-art-98661f23126f407b9097d69037f88438 |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-98661f23126f407b9097d69037f884382025-01-12T12:10:25ZengBMCMolecular Cancer1476-45982025-01-0124111610.1186/s12943-024-02204-7Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinomaWeiwei Chen0Chutian Wu1Yuting Li2Tonghua Wang3Miaoling Huang4Min Wang5Linjing Long6Yanfang Chen7Shufen Feng8Xuyou Liu9Shaohui Tang10Department of Gastroenterology, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, Weifang People’s Hospital, Shandong Second Medical UniversityDepartment of Gastroenterology, Affiliated Hospital of Youjiang Medical University for NationalitiesDepartment of General Practice, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Jinan UniversityDepartment of Gastroenterology, Guangzhou Red Cross Hospital, Jinan UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Jinan UniversityAbstract Background The insulin-like growth factor 2 (IGF2) and H19 are overexpressed in hepatocellular carcinoma (HCC). IGF2-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in IGF2 and H19 overexpression regulation and its role in HCC. Methods Firstly, the effect of miR-483-5p on the expression of IGF2 and H19, and the binding of miR-483-5p to IGF2/H19 enhancer were evaluated in HCC cells. Next, miR-483-5p-mediated IGF2/H19 enhancer activation and its mechanism were investigated in HCC cells. Then, the mechanism by which active IGF2/H19 enhancer mediated by miR-483-5p activate IGF2/H19 promoters was studied in HCC cells. Finally, the effect of MED1 on the expression of IGF2/H19 as well as the malignant phenotype of HCC cells in vitro and in vivo mediated by miR-483-5p was evaluated. Results Mir-483-5p up-regulated IGF2 P2 mRNA-P4 mRNA and H19 expression by binding to IGF2/H19 enhancer resulting in IGF2/H19 enhancer activation in HCC cells. Mechanistically, miR-483-5p increased recruitment of Ago1 and Ago2 at IGF2/H19 enhancer and then activated transcription of IGF2/H19 eRNA by RNA polymerase II and p300, which further induced chromatin loops formation between IGF2/H19 enhancer and IGF2/H19 promoters to activate IGF2/H19 promoters via IGF2/H19 eRNA-MED1-IGF2/H19 promoters complex in HCC cells. In this process, MED1 promoted chromatin loops formation as well as the malignant phenotype of HCC cells in vitro and in vivo mediated by miR-483-5p. Conclusions miR-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via DNA loops, thereby promoting the malignant progression of HCC.https://doi.org/10.1186/s12943-024-02204-7miR-483-5pEnhancerMED1HCC |
| spellingShingle | Weiwei Chen Chutian Wu Yuting Li Tonghua Wang Miaoling Huang Min Wang Linjing Long Yanfang Chen Shufen Feng Xuyou Liu Shaohui Tang Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma Molecular Cancer miR-483-5p Enhancer MED1 HCC |
| title | Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma |
| title_full | Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma |
| title_fullStr | Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma |
| title_full_unstemmed | Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma |
| title_short | Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma |
| title_sort | mir 483 5p mediated activating of igf2 h19 enhancer up regulates igf2 h19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma |
| topic | miR-483-5p Enhancer MED1 HCC |
| url | https://doi.org/10.1186/s12943-024-02204-7 |
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