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Downregulation of miR-503 contributes to the development of drug resistance in ovarian cancer by targeting PI3K p85.
Arch Gynecol Obstet. 2018 03; 297(3):699-707.AG

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.

Authors+Show Affiliations

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. miaojinweibjfc@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29327155

Citation

Wu, Di, et al. "Downregulation of miR-503 Contributes to the Development of Drug Resistance in Ovarian Cancer By Targeting PI3K P85." Archives of Gynecology and Obstetrics, vol. 297, no. 3, 2018, pp. 699-707.
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. 2018;297(3):699-707.
Wu, D., Lu, P., Mi, X., & Miao, J. (2018). Downregulation of miR-503 contributes to the development of drug resistance in ovarian cancer by targeting PI3K p85. Archives of Gynecology and Obstetrics, 297(3), 699-707. https://doi.org/10.1007/s00404-018-4649-0
Wu D, et al. Downregulation of miR-503 Contributes to the Development of Drug Resistance in Ovarian Cancer By Targeting PI3K P85. Arch Gynecol Obstet. 2018;297(3):699-707. PubMed PMID: 29327155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of miR-503 contributes to the development of drug resistance in ovarian cancer by targeting PI3K p85. AU - Wu,Di, AU - Lu,Pan, AU - Mi,Xue, AU - Miao,Jinwei, Y1 - 2018/01/11/ PY - 2017/09/07/received PY - 2018/01/03/accepted PY - 2018/1/13/pubmed PY - 2019/4/6/medline PY - 2018/1/13/entrez KW - Drug resistance KW - Ovarian cancer KW - PI3K KW - miRNA-503 SP - 699 EP - 707 JF - Archives of gynecology and obstetrics JO - Arch. Gynecol. Obstet. VL - 297 IS - 3 N2 - 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. SN - 1432-0711 UR - https://www.unboundmedicine.com/medline/citation/29327155/Downregulation_of_miR_503_contributes_to_the_development_of_drug_resistance_in_ovarian_cancer_by_targeting_PI3K_p85_ L2 - https://dx.doi.org/10.1007/s00404-018-4649-0 DB - PRIME DP - Unbound Medicine ER -