CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure
Abstract CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution in RCC remain elusive. We confirmed the overexpression of circZBTB44 in RCC cells compared to normal kidney cell HK-2. CircZBTB44 knockdown suppressed t...
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| Language: | English |
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BMC
2023-04-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-023-01771-5 |
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| author | Tushuai Li Yue Gu Baocai Xu Kamil Kuca Jie Zhang Wenda Wu |
| author_facet | Tushuai Li Yue Gu Baocai Xu Kamil Kuca Jie Zhang Wenda Wu |
| author_sort | Tushuai Li |
| collection | DOAJ |
| description | Abstract CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution in RCC remain elusive. We confirmed the overexpression of circZBTB44 in RCC cells compared to normal kidney cell HK-2. CircZBTB44 knockdown suppressed the viability, proliferation, and migration of RCC cells and inhibited tumorigenesis in xenograft mouse models. Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) are two RNA binding proteins of circZBTB44. HNRNPC facilitated the translocation of circZBTB44 from nuclei to cytoplasm via m6A modification, facilitating the interaction of IGF2BP3 and circZBTB44 in the cytoplasm of RCC cells. Furthermore, circZBTB44 upregulated Hexokinase 3 (HK3) expression by binding to IGF2BP3 in RCC cells. HK3 exerted oncogenic effects on RCC cell malignant behaviors and tumor growth. In the co-culture of RCC cells with macrophages, circZBTB44 promoted M2 polarization of macrophages by up-regulating HK3. In summary, HNRNPC mediated circZBTB44 interaction with IGF2BP3 to up-regulate HK3, promoting the proliferation and migration of RCC cells in vitro and tumorigenesis in vivo. The results of the study shed new light on the targeted therapy of RCC. |
| format | Article |
| id | doaj-art-df061c58515748dba9b9217e9aa4a271 |
| institution | DOAJ |
| issn | 1476-4598 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | BMC |
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| series | Molecular Cancer |
| spelling | doaj-art-df061c58515748dba9b9217e9aa4a2712025-08-20T02:49:26ZengBMCMolecular Cancer1476-45982023-04-0122111410.1186/s12943-023-01771-5CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structureTushuai Li0Yue Gu1Baocai Xu2Kamil Kuca3Jie Zhang4Wenda Wu5School of Food and Biological Engineering, Hefei University of TechnologyKey Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical UniversitySchool of Food and Biological Engineering, Hefei University of TechnologyDepartment of Chemistry, Faculty of Science, University of Hradec KraloveSchool of Biology and Food Engineering, Changshu Institute of TechnologySchool of Food and Biological Engineering, Hefei University of TechnologyAbstract CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution in RCC remain elusive. We confirmed the overexpression of circZBTB44 in RCC cells compared to normal kidney cell HK-2. CircZBTB44 knockdown suppressed the viability, proliferation, and migration of RCC cells and inhibited tumorigenesis in xenograft mouse models. Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) are two RNA binding proteins of circZBTB44. HNRNPC facilitated the translocation of circZBTB44 from nuclei to cytoplasm via m6A modification, facilitating the interaction of IGF2BP3 and circZBTB44 in the cytoplasm of RCC cells. Furthermore, circZBTB44 upregulated Hexokinase 3 (HK3) expression by binding to IGF2BP3 in RCC cells. HK3 exerted oncogenic effects on RCC cell malignant behaviors and tumor growth. In the co-culture of RCC cells with macrophages, circZBTB44 promoted M2 polarization of macrophages by up-regulating HK3. In summary, HNRNPC mediated circZBTB44 interaction with IGF2BP3 to up-regulate HK3, promoting the proliferation and migration of RCC cells in vitro and tumorigenesis in vivo. The results of the study shed new light on the targeted therapy of RCC.https://doi.org/10.1186/s12943-023-01771-5circZBTB44HK3Renal carcinomaIGF2BP3HNRNPCm6A |
| spellingShingle | Tushuai Li Yue Gu Baocai Xu Kamil Kuca Jie Zhang Wenda Wu CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure Molecular Cancer circZBTB44 HK3 Renal carcinoma IGF2BP3 HNRNPC m6A |
| title | CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure |
| title_full | CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure |
| title_fullStr | CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure |
| title_full_unstemmed | CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure |
| title_short | CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure |
| title_sort | circzbtb44 promotes renal carcinoma progression by stabilizing hk3 mrna structure |
| topic | circZBTB44 HK3 Renal carcinoma IGF2BP3 HNRNPC m6A |
| url | https://doi.org/10.1186/s12943-023-01771-5 |
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