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MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells.
Tumour Biol. 2014 Dec; 35(12):12369-78.TB

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for the advanced ovarian cancer, but resistance to cisplatin remains a major obstacle to successful treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in disease processes, including the development of drug resistance. In this study, we found miR-449a were significantly downregulated in the cisplatin-resistant ovarian cell lines SKOV3/DDP and A2780/DDP, compared with their sensitive parent line SKOV3 and A2780, respectively. The overexpression of miR-449a increased cisplatin sensitivity of SKOV3/DDP and A2780/DDP cells by inhibiting proliferation and promoting apoptosis. The luciferase assay confirmed that miR-449a functioned through suppressing NOTCH1 directly. Concordantly, BALB/c nude mice that were injected intraperitoneally with SKOV3/DDP cells transfected with miR-449a mimics exhibited enhanced cisplatin sensitivity in vivo. Taken together, these results suggest that the ectopic expression of miR-449a may be a promising therapeutic strategy for the management of cisplatin resistance in ovarian cancer.

Authors+Show Affiliations

Department of Gynaecology and Obstetrics, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25179844

Citation

Zhou, Yanqi, et al. "MicroRNA-449a Reduces Cell Survival and Enhances Cisplatin-induced Cytotoxicity Via Downregulation of NOTCH1 in Ovarian Cancer Cells." Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine, vol. 35, no. 12, 2014, pp. 12369-78.
Zhou Y, Chen Q, Qin R, et al. MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. Tumour Biol. 2014;35(12):12369-78.
Zhou, Y., Chen, Q., Qin, R., Zhang, K., & Li, H. (2014). MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine, 35(12), 12369-78. https://doi.org/10.1007/s13277-014-2551-3
Zhou Y, et al. MicroRNA-449a Reduces Cell Survival and Enhances Cisplatin-induced Cytotoxicity Via Downregulation of NOTCH1 in Ovarian Cancer Cells. Tumour Biol. 2014;35(12):12369-78. PubMed PMID: 25179844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. AU - Zhou,Yanqi, AU - Chen,Qiaoyun, AU - Qin,Rong, AU - Zhang,Kaifeng, AU - Li,Hao, Y1 - 2014/09/02/ PY - 2014/06/26/received PY - 2014/08/25/accepted PY - 2014/9/3/entrez PY - 2014/9/3/pubmed PY - 2015/3/11/medline SP - 12369 EP - 78 JF - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JO - Tumour Biol. VL - 35 IS - 12 N2 - Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for the advanced ovarian cancer, but resistance to cisplatin remains a major obstacle to successful treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in disease processes, including the development of drug resistance. In this study, we found miR-449a were significantly downregulated in the cisplatin-resistant ovarian cell lines SKOV3/DDP and A2780/DDP, compared with their sensitive parent line SKOV3 and A2780, respectively. The overexpression of miR-449a increased cisplatin sensitivity of SKOV3/DDP and A2780/DDP cells by inhibiting proliferation and promoting apoptosis. The luciferase assay confirmed that miR-449a functioned through suppressing NOTCH1 directly. Concordantly, BALB/c nude mice that were injected intraperitoneally with SKOV3/DDP cells transfected with miR-449a mimics exhibited enhanced cisplatin sensitivity in vivo. Taken together, these results suggest that the ectopic expression of miR-449a may be a promising therapeutic strategy for the management of cisplatin resistance in ovarian cancer. SN - 1423-0380 UR - https://www.unboundmedicine.com/medline/citation/25179844/MicroRNA_449a_reduces_cell_survival_and_enhances_cisplatin_induced_cytotoxicity_via_downregulation_of_NOTCH1_in_ovarian_cancer_cells_ L2 - https://link.springer.com/article/10.1007/s13277-014-2551-3 DB - PRIME DP - Unbound Medicine ER -