CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA
Abstract Triple-negative breast cancer (TNBC) is a molecular subtype with an unfavorable prognosis, and metastasis is the main reason for the failure of clinical treatment. However, the expression profile and regulatory function of circRNAs in TNBC progression are not fully understood. Herein, we pe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-05-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01055-9 |
| _version_ | 1818206883503144960 |
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| author | Xiaojin Song Bing Chen Yiran Liang Yaming Li Hanwen Zhang Dianwen Han Yajie Wang Fangzhou Ye Lijuan Wang Wenjing Zhao Qifeng Yang |
| author_facet | Xiaojin Song Bing Chen Yiran Liang Yaming Li Hanwen Zhang Dianwen Han Yajie Wang Fangzhou Ye Lijuan Wang Wenjing Zhao Qifeng Yang |
| author_sort | Xiaojin Song |
| collection | DOAJ |
| description | Abstract Triple-negative breast cancer (TNBC) is a molecular subtype with an unfavorable prognosis, and metastasis is the main reason for the failure of clinical treatment. However, the expression profile and regulatory function of circRNAs in TNBC progression are not fully understood. Herein, we performed high-throughput RNA-seq in paired breast cancer tissues and adjacent normal tissues and discovered a novel circRNA, circEIF3H, which was upregulated in breast cancer tissues. Large cohort survival analysis confirmed the association between high circEIF3H expression and poor prognosis of TNBC, indicating the vital function of circEIF3H in TNBC progression. Then we conducted both in vitro and in vivo experiments which illustrated that circEIF3H was essential for TNBC proliferation and metastasis. Further experiments showed that circEIF3H did not function as a microRNA sponge as in the most well-established pathway, but as a scaffold for IGF2BP2 and HuR to regulate the mRNA stability of HSPD1, RBM8A, and G3BP1. Our findings provide insight into a novel circRNA, circEIF3H, with significant cancer-promoting function via serving as a scaffold for IGF2BP2/HuR. These results identified circEIF3H as a potential target for developing individualized therapy of TNBC in the approaching future. |
| first_indexed | 2024-12-12T04:20:06Z |
| format | Article |
| id | doaj.art-7868632f1814480f92848f1c44b90e53 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-12T04:20:06Z |
| publishDate | 2022-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-7868632f1814480f92848f1c44b90e532022-12-22T00:38:21ZengNature Publishing GroupCell Death Discovery2058-77162022-05-018111210.1038/s41420-022-01055-9CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNAXiaojin Song0Bing Chen1Yiran Liang2Yaming Li3Hanwen Zhang4Dianwen Han5Yajie Wang6Fangzhou Ye7Lijuan Wang8Wenjing Zhao9Qifeng Yang10Department of Breast Surgery, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityAbstract Triple-negative breast cancer (TNBC) is a molecular subtype with an unfavorable prognosis, and metastasis is the main reason for the failure of clinical treatment. However, the expression profile and regulatory function of circRNAs in TNBC progression are not fully understood. Herein, we performed high-throughput RNA-seq in paired breast cancer tissues and adjacent normal tissues and discovered a novel circRNA, circEIF3H, which was upregulated in breast cancer tissues. Large cohort survival analysis confirmed the association between high circEIF3H expression and poor prognosis of TNBC, indicating the vital function of circEIF3H in TNBC progression. Then we conducted both in vitro and in vivo experiments which illustrated that circEIF3H was essential for TNBC proliferation and metastasis. Further experiments showed that circEIF3H did not function as a microRNA sponge as in the most well-established pathway, but as a scaffold for IGF2BP2 and HuR to regulate the mRNA stability of HSPD1, RBM8A, and G3BP1. Our findings provide insight into a novel circRNA, circEIF3H, with significant cancer-promoting function via serving as a scaffold for IGF2BP2/HuR. These results identified circEIF3H as a potential target for developing individualized therapy of TNBC in the approaching future.https://doi.org/10.1038/s41420-022-01055-9 |
| spellingShingle | Xiaojin Song Bing Chen Yiran Liang Yaming Li Hanwen Zhang Dianwen Han Yajie Wang Fangzhou Ye Lijuan Wang Wenjing Zhao Qifeng Yang CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA Cell Death Discovery |
| title | CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA |
| title_full | CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA |
| title_fullStr | CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA |
| title_full_unstemmed | CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA |
| title_short | CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA |
| title_sort | circeif3h igf2bp2 hur scaffold complex promotes tnbc progression via stabilizing hspd1 rbm8a g3bp1 mrna |
| url | https://doi.org/10.1038/s41420-022-01055-9 |
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