Exosomal Mir-210-3p Promotes Chemoresistance and Stem Cell Properties in Cervical Cancer by Targeting FBXO31

Xiaoling TANG; Bangfang XIE; Hailong HUANG

doi:10.12259/j.issn.2095-610X.S20250707

Volume 46 Issue 7

Jul. 2025

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Xiaoling TANG, Bangfang XIE, Hailong HUANG. Exosomal Mir-210-3p Promotes Chemoresistance and Stem Cell Properties in Cervical Cancer by Targeting FBXO31[J]. Journal of Kunming Medical University, 2025, 46(7): 54-64. doi: 10.12259/j.issn.2095-610X.S20250707

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Xiaoling TANG, Bangfang XIE, Hailong HUANG. Exosomal Mir-210-3p Promotes Chemoresistance and Stem Cell Properties in Cervical Cancer by Targeting FBXO31[J]. Journal of Kunming Medical University, 2025, 46(7): 54-64. doi: 10.12259/j.issn.2095-610X.S20250707

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Exosomal Mir-210-3p Promotes Chemoresistance and Stem Cell Properties in Cervical Cancer by Targeting FBXO31

doi: 10.12259/j.issn.2095-610X.S20250707

Department of Obstetrics and Gynecology，People’s Hospital of Qingbaijiang District，Chengdu City，Chengdu Sichuan 610300，China

Received Date: 2025-04-09
Publish Date: 2025-07-21

Abstract

Abstract

Objective To investigate the role of exosomal microRNA （miRNA） miR-210-3p in chemoresistance and stem cell property formation in cervical cancer, and to elucidate its underlying mechanism through targeting of F-box protein 31 （FBXO31）. Methods Exosomes were isolated from cisplatin-sensitive HeLa cells and cisplatin-resistant HeLa/DDP cells via ultracentrifugation, and their uptake by HeLa/DDP cells was verified using the PKH26 red fluorescent labeling method. HeLa cells were transfected with NC inhibitor, miR-210-3p inhibitor alone, or in combination with si-NC and si-FBXO31. After 24 hours of transfection, exosomes were extracted and co-cultured with HeLa/DDP cells for 48 hours. Consequently, HeLa/DDP cells were divided into five groups: the Ctrl group （PBS blank control）, the NC inhibitor group, the miR-210-3p inhibitor group, the miR-210-3p inhibitor+si-NC group and the miR-210-3p inhibitor+si-FBXO31 group. RT-qPCR was used to measure miR-210-3p and FBXO31 expression levels. The half-maximal inhibitory concentration （IC₅₀） of cisplatin was determined using the MTT assay. Stem cell properties were assessed via tumor sphere formation assays. Western blot analysis was performed to detect the protein expression of FBXO31 and stem cell markers （e.g., SOX2, OCT4, NANOG）. The targeting relationship between miR-210-3p and FBXO31 was validated using dual-luciferase reporter assays. The effect of exosomal miR-210-3p on the metastasis of cervical cancer in vivo was evaluated by nude mice xenograft tumor. Resuts Compared with human normal cervical epithelial cells （HCeEpiC）, miR-210-3p expression was significantly upregulated in cervical cancer cell lines （HeLa, HT3, C33A, and CaSki）, while FBXO31 expression was significantly downregulated （P < 0.05）. HeLa/DDP cells （cisplatin-resistant） exhibited significantly higher miR-210-3p expression levels and IC₅₀ values for cisplatin compared with parental HeLa cells （P < 0.05）, and HeLa exosomes were efficiently taken up by HeLa/DDP cells. Compared with the NC inhibitor groupThe miR-210-3p inhibitor group showed significantly reduced expression levels of miR-210-3p, OCT4, SOX2, and NANOG, as well as a significantly lower IC50 （P < 0.05）, while FBXO31 expression was significantly increased （P < 0.05）. Compared with the miR-210-3p inhibitor + si-NC group, the miR-210-3p inhibitor + si-FBXO31 group exhibited significantly decreased FBXO31 expression （P < 0.05） and increased IC50, Oct-4, SOX2, and NANOG expression （P < 0.05）. Compared with the control group and the empty vector group, the tumor weight and volume were significantly lower in the miR-210-3p than in the control and empty vector groups （P < 0.05）. Conclusion Exosomal miR-210-3p promotes chemoresistance to DDP and enhances stem cell-like properties in CC cells by directly targeting and inhibiting FBXO31.
- Exosome,
- MiR-210-3p,
- Chemoresistance,
- Stem cell properties,
- FBXO31,
- Cervical cancer

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