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Updated: Apr 23, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Deregulation of miR-128 in ovarian cancer promotes cisplatin resistance
1Departments of *Gynecology and Obstetrics, and †Anesthesiology, the Military General Hospital of Beijing PLA, Beijng, China.
Objective:
Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.
Materials And Methods:
The expression of miR-128 RNA and its targeted genes, the polycomb ring finger oncogene Bmi-1 and ATP-binding cassette subfamily C member 5 (ABCC5), were investigated in the epithelial ovarian cancer cells and ovarian carcinomas.
Results:
miR-128 expression was significantly reduced in the cisplatin-resistant human epithelial ovarian cancer cell line SKOV3/CP compared with parental SKOV3 cells and decreased upon treatment with cisplatin in a concentration-dependent manner in SKOV3, OVCAR3, and PEO14 cells. Overexpression of miR-128 resensitized SKOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant-related proteins ABCC5 and Bmi-1, whereas miR-128 inhibitors increased cisplatin resistance in SKOV3 cells. Cisplatin combined with miR-128 agomirs inhibited the growth of SKOV3/CP xenograft tumors more effectively than cisplatin alone. Diminished expression of ABCC5 and Bmi-1 and higher cisplatin concentrations were observed in tumor tissue of mice treated with miR-128 agomirs in addition to cisplatin.
Conclusions:
Taken together, our findings suggest that miR-128 may act as a promising therapeutic target for improvement of tumor sensitivity to cisplatin.
Insights
MicroRNA 128 (miR-128) is reduced in cisplatin-resistant ovarian cancer. Restoring miR-128 resensitizes cancer cells to chemotherapy and inhibits tumor growth, suggesting miR-128 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Platinum-based chemotherapy is standard for advanced ovarian cancer but often fails due to drug resistance.
- MicroRNAs play a role in chemoresistance across various cancers.
- The specific role of miR-128 in cisplatin resistance in ovarian cancer requires further investigation.
Purpose of the Study:
- To investigate the role of miR-128 in the development of cisplatin resistance in ovarian cancer.
- To explore miR-128 as a potential therapeutic target for overcoming chemoresistance.
Main Methods:
- Assessed miR-128 expression in cisplatin-resistant and sensitive ovarian cancer cells and tissues.
- Investigated the impact of miR-128 modulation (overexpression and inhibition) on cisplatin sensitivity.
- Examined the expression of targeted genes, Bmi-1 and ABCC5, in relation to miR-128 levels.
- Evaluated the efficacy of combined cisplatin and miR-128 agomir treatment in a xenograft mouse model.
Main Results:
- miR-128 expression was significantly lower in cisplatin-resistant ovarian cancer cells and decreased with cisplatin treatment.
- Overexpression of miR-128 restored sensitivity to cisplatin in resistant cells and reduced Bmi-1 and ABCC5 expression.
- miR-128 inhibition increased cisplatin resistance.
- Combination therapy with cisplatin and miR-128 agomirs showed enhanced tumor growth inhibition in vivo.
Conclusions:
- miR-128 plays a crucial role in modulating cisplatin sensitivity in ovarian cancer.
- Reduced miR-128 expression contributes to chemoresistance by upregulating Bmi-1 and ABCC5.
- miR-128 represents a promising therapeutic target to enhance the efficacy of cisplatin treatment in ovarian cancer.
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