2. Academic Validation
  3. Circ_0057582 inhibits breast cancer progression via hnRNPF/YAP/SOX9 axis and M2 polarization in TAMs by autophagic degradation of ISG15

Circ_0057582 inhibits breast cancer progression via hnRNPF/YAP/SOX9 axis and M2 polarization in TAMs by autophagic degradation of ISG15

  • Biochem Pharmacol. 2026 Jan;243(Pt 2):117543. doi: 10.1016/j.bcp.2025.117543.
Yuexin Zhao 1,  Shiliang Xu 2,  Xiao Li 1,  Xixi Wu 3,  Lingxia Wang 1,  Bo Wang 4,  Huan Yang 5
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China; Department of HLA Laboratory, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 3 Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China; The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
  • 4 Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: [email protected].
  • 5 Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: [email protected].
PMID: 41241017 DOI: 10.1016/j.bcp.2025.117543
Abstract

Circular RNA plays a critical role in tumorigenesis by regulating tumor cell behavior and the tumor microenvironment, and represents a promising biomarker for early Cancer diagnosis, treatment response, and prognosis. However, the function and mechanism of circ_0057582 in breast Cancer remain unclear. In this study, in vitro and in vivo assays demonstrated that circ_0057582 is downregulated in breast Cancer tissues and serum, and its overexpression suppresses tumor growth. Mechanistically, circ_0057582 binds to hnRNPF, modulating alternative splicing and reducing YAP expression, which subsequently downregulates SOX9. Furthermore, circ_0057582 promotes ISG15 degradation via Autophagy, thereby reducing secreted ISG15 and inhibiting M2-type tumor-associated macrophage polarization. These findings reveal the tumor-suppressive role of circ_0057582 in breast Cancer and elucidate its underlying molecular mechanisms.

Keywords

Autophagy; Breast cancer; Circ_0057582; Progression; TAMs.

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