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.

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove 50003 Czech Republic

Key Laboratory of Anti inflammatory and Immune Medicine Ministry of Education Institute of Clinical Pharmacology Anhui Medical University Hefei 230032 China

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China

School of Biology and Food Engineering Changshu Institute of Technology 99 Southern Sanhuan Road Suzhou 215500 China

School of Food and Biological Engineering Hefei University of Technology 420 Feicui Road Hefei 230009 China

Wuxi School of Medicine Jiangnan University Wuxi 214013 China

Mol Cancer. 2025 Mar 27;24(1):98. doi: 10.1186/s12943-025-02307-9. PubMed

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Correction: CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure