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ARTICLE

MicroRNA320e Augments the Synthetic Lethality of Olaparib by Regulating the PI3K-AKT-mTOR Pathway

Wei Zheng1,#, Qianlong Meng1,2,#, Yunhan Deng1, Ruizhen Liu1, Siyu Bai1, Longyu Jia1, Jing Wang3,4,*, Huimin Bai1,*
1 Department of Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
2 Department of Diagnostics of Clinical Laboratory, Zhejiang Hospital, Hangzhou, China
3 Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
4 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
* Corresponding Author: Jing Wang. Email: email; Huimin Bai. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Innovative Diagnostic Strategies in Gynecological Cancer Research)

Oncology Research https://doi.org/10.32604/or.2026.081656

Received 06 March 2026; Accepted 11 June 2026; Published online 27 July 2026

Abstract

Objectives: Given the increasing drug resistance in ovarian cancer (OC), the use of poly ADP-ribose polymerase inhibitors (PARPi) for treating homologous recombination repair defects (HRD) has encountered new challenges. MicroRNA320e (miR-320e) exerts a negative regulatory role in the progression of multiple cancers. This study aimed to investigate the association between miR-320e and drug resistance in ovarian cancer. Methods: The Cell Counting Kit-8 (CCK-8) assay, migration and invasion assays, and colony formation assay were employed to evaluate the proliferation, migration, and invasion abilities of cells. Western blot (WB) analysis was used to verify the expression levels of proteins related to the relevant signaling pathways in cells. The xenograft subcutaneous tumor model was established to investigate the effect of miR-320e on in vivo tumor growth. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to detect the expression levels of related proteins and miR-320e in tumor tissues from patients and animals, respectively. Results: miR-320e was overexpressed in both A2780 and SKOV3 cells. The results showed that transfection with miR-320e significantly reduced cell proliferation, invasion, and migration, while enhancing autophagy and apoptosis. Additionally, the PI3K-AKT-mTOR signaling pathway was significantly inhibited in the treatment groups. In nude mouse models, overexpression of miR-320e also significantly suppressed tumor growth. These findings indicate that overexpression of miR-320e enhances the sensitivity of OC cells to olaparib therapy. Conclusion: In conclusion, miR-320e overexpression significantly inhibits the malignancy of ovarian cancer and increases the sensitivity of ovarian cancer cells to olaparib.

Keywords

MicroRNA320e (miR-320e); poly ADP-ribose polymerase inhibitors (PARPi); PI3K-AKT-mTOR; olaparib; fibronectin 1 (FN1)

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