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Downregulation of miR-503 contributes to the development of drug resistance in ovarian cancer by targeting PI3K p85

  • General Gynecology
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Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

Cisplatin is an important chemotherapeutic agent frequently used in the treatment of ovarian cancer. However, resistance to cisplatin is an obstacle to the treatment of ovarian cancer. Recently, many studies have demonstrated that microRNAs (miRNAs) are involved in the drug resistance of ovarian cancer cells. In this study, we explored the role of miR-503 in cisplatin-resistant ovarian cancer.

Materials and Methods

To investigate the relationship between miR-503 expression and the sensitivity of ovarian cancer cells to cisplatin, the cells were transfected with miR-503 mimics/inhibitors. The relative expression of miR-503 RNA and its targeted gene PI3K mRNA were detected by real-time PCR (RT-PCR). Western blot was used to measure relevant protein levels. Flow cytometry and CCK-8 assay were used to analyze cell proliferation and apoptosis.

Results

MiR-503 expression was significantly downregulated in cisplatin-resistant ovarian cancer cell line SKOV3/DDP compared with parental SKOV3. Over-expression and knock-down of miR-503 partially regulated apoptotic activity and changed the cisplatin resistance of ovarian cancer cells. In exploring the underlying mechanisms of miR-503 in ovarian cancer cells’ resistance to cisplatin, we found that miR-503 can directly target PI3K p85 and participates in the regulation of the PI3K/Akt signaling pathway. In vivo, miR-503 agomirs combined with cisplatin treatment significantly reduced the growth of tumors compared with cisplatin alone.

Conclusions

Our data suggest that miR-503 might be a sensitizer to cisplatin treatment in ovarian cancer by targeting PI3K p85, thus giving a new insight into developing therapeutic strategies to overcome cisplatin resistance in ovarian cancer.

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Funding

This study was funded by Beijing Natural Science Foundation (no. 7162063).

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

    Di Wu, Pan Lu, Xue Mi & Jinwei Miao

Authors
  1. Di Wu
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  2. Pan Lu
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  3. Xue Mi
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  4. Jinwei Miao
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Contributions

DW: Data analysis, Data collection, Manuscript writing. PL: Data collection. XM: Data collection. JM: Project development.

Corresponding author

Correspondence to Jinwei Miao.

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Conflict of interest

Di Wu declares that she has no conflict of interest. Pan Lu declares that she has no conflict of interest. Xue Mi declares that she has no conflict of interest. Jinwei Miao declares that she has no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Wu, D., Lu, P., Mi, X. et al. Downregulation of miR-503 contributes to the development of drug resistance in ovarian cancer by targeting PI3K p85. Arch Gynecol Obstet 297, 699–707 (2018). https://doi.org/10.1007/s00404-018-4649-0

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  • DOI: https://doi.org/10.1007/s00404-018-4649-0

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