2. Academic Validation
  3. Targeting circSFPQ_008/SFPQ/BRCA1 axis for overcoming platinum resistance in ovarian cancer

Targeting circSFPQ_008/SFPQ/BRCA1 axis for overcoming platinum resistance in ovarian cancer

  • MedScience. 2026 Mar 31. doi: 10.1007/s11684-026-1201-7.
Yinan Jiang # 1 2,  Dongmei Zhou # 1 2,  Yan Liu # 1 2,  Baixue Li 1 2,  Renci Liu 1 2,  Jianqi Li 1 2,  Xiujie Sheng 3 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
  • 2 Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
  • 3 Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China. [email protected].
  • 4 Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China. [email protected].
  • # Contributed equally.
PMID: 41917322 DOI: 10.1007/s11684-026-1201-7
Abstract

Platinum resistance is the main cause of treatment failure in ovarian Cancer. BRCA1/2-mediated DNA damage repairment is an important factor contributing to platinum resistance in ovarian Cancer. Altering the expression levels of BRCA1/2 will affect the platinum sensitivity of ovarian Cancer. We used proteomics to screen out SFPQ, which bound to BRCA1 with a high abundance. However, the role and potential mechanism of SFPQ in the progression of ovarian Cancer remain unclear. Through immunohistochemical staining, we found that SFPQ was overexpressed in ovarian Cancer tissues and associated with poor prognosis of patients. Functional analysis showed that SFPQ binds to BRCA1 and inhibits its ubiquitination and degradation, increases the expression level of BRCA1, and promotes platinum resistance of ovarian Cancer. Exploration of the upstream mechanism revealed that hsa_circSFPQ_008, which was derived from the SFPQ parental gene, recruits HDAC1 to modify H3K27Ac of the SFPQ promoter and regulates its expression. This study reveals a novel regulatory mechanism by which SFPQ is involved in platinum resistance of ovarian Cancer, providing a new theoretical basis for the individualized and precise treatment of ovarian Cancer.

Keywords

DNA damage repair; SFPQ; ovarian cancer; platinum resistance.

Figures
Products
Inhibitors & Agonists
Other Products