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Updated: Apr 2, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Targeting circSFPQ_008/SFPQ/BRCA1 axis for overcoming platinum resistance in ovarian cancer
Yinan Jiang1,2, Dongmei Zhou1,2, Yan Liu1,2
1Department 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.
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.
Insights
this study identifies SFPQ as a key driver of platinum resistance in ovarian cancer by stabilizing BRCA1. Overexpression of SFPQ, regulated by a circRNA, predicts poor prognosis and offers a new therapeutic target for ovarian cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Platinum-based chemotherapy is a cornerstone treatment for ovarian cancer.
- Platinum resistance is a major cause of treatment failure and poor patient outcomes.
- BRCA1/2 mutations and their role in DNA repair are critical factors in platinum sensitivity.
Purpose of the Study:
- To elucidate the role and mechanism of SFPQ in ovarian cancer progression and platinum resistance.
- To identify novel regulatory pathways involved in ovarian cancer treatment failure.
- To explore potential therapeutic targets for overcoming platinum resistance.
Main Methods:
- Proteomic screening to identify BRCA1-interacting proteins.
- Immunohistochemical staining to assess SFPQ expression in patient tissues.
- Functional assays to determine SFPQ's effect on BRCA1 stability and ubiquitination.
- Investigation of upstream regulatory mechanisms involving circular RNA (hsa_circSFPQ_008) and histone modification.
Main Results:
- SFPQ was found to be overexpressed in ovarian cancer tissues and correlated with poor prognosis.
- SFPQ binds to BRCA1, inhibiting its ubiquitination and degradation, thereby increasing BRCA1 levels.
- This interaction promotes platinum resistance in ovarian cancer.
- A novel regulatory pathway was identified where hsa_circSFPQ_008 recruits HDAC1 to regulate SFPQ promoter activity and expression.
Conclusions:
- SFPQ plays a significant role in promoting platinum resistance in ovarian cancer by stabilizing BRCA1.
- The SFPQ regulatory axis, involving hsa_circSFPQ_008 and epigenetic modifications, represents a novel mechanism in ovarian cancer.
- Targeting SFPQ or its regulatory pathway may offer a new strategy for individualized and precise treatment of ovarian cancer.
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