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Published on: August 2, 2024
MiR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer
Bing Li1, Xuejie Xu1, Linlin Zheng1
1Department of Medical Oncology, the Affiliated Hospital of Putian University, Putian, 351100, Fujian province, China.
Objective:
The mechanisms of ovarian cancer generate chemotherapy resistance are still unclear. This study aimed to explore the role of microRNA (miR)-590-5p in regulating hMSH2 expression and cisplatin resistance in ovarian cancer.
Methods:
MiR-590-5p was identified as a regulator of hMSH2 with miRDB database and Target Scan database. Then cisplatin sensitive cell line (SKOV3) and resistant cell line (SKOV3-DDP) of ovarian cancer were cultured for cell functional assay and molecular biology assay. The expression levels of MiR-590-5p and hMSH2 were compared between the two cell lines. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between miR-590-5p and hMSH2. CCK-8 assay and cell apoptosis assay were utilized to assess the role of MiR-590-5p and hMSH2 in cell viability under cisplatin.
Results:
The expression of hMSH2 was significantly decreased, and miR-590-5p was significantly up-regulated in SKOV3-DDP. Up-regulation of hMSH2 weakened the viability of SKOV3 and SKOV3-DDP cell under cisplatin. Transfection with miR‑590-5p mimics reduced the expression of hMSH2 and enhanced the viability of ovarian cancer cells under cisplatin, whereas inhibition of miR‑590-5p increased the expression of hMSH2, and decreased ovarian cancer cells' viability under cisplatin. Furthermore, luciferase reporter assay showed that hMSH2 was a direct target of miR-590-5p.
Conclusion:
The present study demonstrates that miR‑590-5p promotes cisplatin resistance of ovarian cancer via negatively regulating hMSH2 expression. Inhibition of miR‑590-5p decreases ovarian cancer cells' viability under cisplatin. Thus miR‑590-5p and hMSH2 may serve as therapeutic targets for cisplatin resistant ovarian cancer.
Insights
MicroRNA-590-5p promotes cisplatin resistance in ovarian cancer by downregulating hMSH2. Inhibiting microRNA-590-5p can decrease cancer cell viability, suggesting therapeutic potential for hMSH2 and microRNA-590-5p in treating resistant ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer chemotherapy resistance mechanisms remain unclear.
- MicroRNAs play crucial roles in cancer development and drug resistance.
Purpose of the Study:
- To investigate the role of microRNA-590-5p (miR-590-5p) in regulating hMSH2 expression.
- To explore the impact of miR-590-5p and hMSH2 on cisplatin resistance in ovarian cancer.
Main Methods:
- Bioinformatic prediction identified miR-590-5p as an hMSH2 regulator.
- Ovarian cancer cell lines (sensitive SKOV3, resistant SKOV3-DDP) were used for functional and molecular assays.
- Dual luciferase reporter assay confirmed the direct targeting of hMSH2 by miR-590-5p.
Main Results:
- miR-590-5p was upregulated, and hMSH2 was downregulated in cisplatin-resistant cells.
- hMSH2 upregulation weakened cell viability under cisplatin treatment.
- miR-590-5p mimics enhanced cell viability, while inhibition decreased it, confirming its role in cisplatin resistance.
Conclusions:
- miR-590-5p promotes cisplatin resistance in ovarian cancer by negatively regulating hMSH2.
- Inhibition of miR-590-5p reduces ovarian cancer cell viability in the presence of cisplatin.
- miR-590-5p and hMSH2 represent potential therapeutic targets for cisplatin-resistant ovarian cancer.
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