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AS-IV inhibits the progression of ovarian cancer by targeting the circ_0124787/miR-6875-3p/IL-1β axis
Nan Fu1, Siyue Zhang2, Ziyi Xiao2
1Department of Gynecologic Oncology, Cancer Hospital Affiliated to Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210009, China; Yili Kazakh Autonomous Prefecture Maternal and Child Health Hospital, Yili, Xinjiang 835100, China.
Background:
Astragaloside IV (AS-IV), a bioactive saponin from Astragalus membranaceus, demonstrates strong anti-tumor effects across various cancers by modulating circular RNAs (circRNAs).
Methods:
Utilizing gene microarray analysis, we identified circ_0124787 as the most abundantly expressed circRNA in ovarian carcinoma tissues. ELISA assays showed that the secretion of IL-1β was significantly increased in the supernatants of SKOV3 and ID8 ovarian cancer cell lines which overexpressing circ_0124787. As a pivotal pro-inflammatory cytokine, IL-1β enhances γδT17 cell proliferation and amplifies inflammatory signaling, which promotes the tumor progression. TargetScan predicted miR-6875-3p as a putative target of circ_0124787, and this prediction was validated by dual-luciferase reporter assays. Functional studies demonstrated that circ_0124787 acts as a competitive endogenous RNA (ceRNA) by sponging miR-6875-3p, thereby derepressing its downstream effector IL-1β. Critically, inhibition of miR-6875-3p completely abolished the anti-tumor efficacy of AS-IV, thereby establishing the indispensability of this circRNA-miRNA axis for its therapeutic activity.
Results:
Our results describe a novel AS-IV/circ_0124787/miR-6875-3p/IL-1β pathway that can decrease the proportion of γδT17 cell to suppress ovarian cancer.
Insights
Astragaloside IV (AS-IV) suppresses ovarian cancer by regulating a pathway involving circ_0124787, miR-6875-3p, and IL-1β. This mechanism reduces pro-tumorigenic γδT17 cells, highlighting a novel therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Astragaloside IV (AS-IV), a saponin from Astragalus membranaceus, exhibits anti-tumor properties.
- Circular RNAs (circRNAs) play a role in cancer progression and are modulated by AS-IV.
Purpose of the Study:
- To elucidate the mechanism by which AS-IV exerts anti-tumor effects in ovarian cancer.
- To identify key circRNAs and their interactions in AS-IV's therapeutic pathway.
Main Methods:
- Gene microarray analysis to identify differentially expressed circRNAs in ovarian cancer.
- ELISA assays to measure IL-1β secretion.
- Dual-luciferase reporter assays to validate circRNA-miRNA interactions.
- Functional studies to assess the role of the circRNA-miRNA axis in AS-IV's efficacy.
Main Results:
- Circ_0124787 was identified as a highly expressed circRNA in ovarian carcinoma.
- Overexpression of circ_0124787 increased IL-1β secretion, promoting γδT17 cell proliferation and tumor progression.
- Circ_0124787 functions as a competitive endogenous RNA (ceRNA) by sponging miR-6875-3p, leading to IL-1β upregulation.
- AS-IV's anti-tumor effect is dependent on the circ_0124787/miR-6875-3p pathway.
Conclusions:
- A novel pathway involving AS-IV, circ_0124787, miR-6875-3p, and IL-1β was identified.
- This pathway suppresses ovarian cancer by decreasing γδT17 cell populations.
- The findings suggest a new therapeutic strategy targeting this axis for ovarian cancer treatment.
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