The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer
| Autor: | Kevin Blansit, Tuyen K. Kiet, John K. Chan, Gabriel Wong, A. Sherman, Lilly Y.W. Bourguignon, Christine Earle |
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| Rok vydání: | 2013 |
| Předmět: |
Apoptosis Inhibitor
Antineoplastic Agents Apoptosis Drug resistance medicine.disease_cause Transfection Annexin Cell Line Tumor microRNA Medicine Humans Ovarian Neoplasms Gene knockdown business.industry Obstetrics and Gynecology medicine.disease Molecular biology MicroRNAs Oncology Drug Resistance Neoplasm Cancer research Female Cisplatin business Ovarian cancer Carcinogenesis |
| Zdroj: | Gynecologic oncology. 132(3) |
| ISSN: | 1095-6859 |
| Popis: | Background MicroRNAs have been implicated in tumorigenesis, drug resistance, and prognosis in cancer. We investigated the role of microRNA-21 ( miR-21 ) in regulating ovarian cancer drug resistance. Methods We used parental and cisplatin resistant ovarian cell lines to demonstrate the role of miR-21 in drug resistance and investigated the gene targets of miR-21 . Fresh tumor specimens were used to validate our in vitro findings. Results Cisplatin resistant ovarian cells were four-fold more resistant compared to the parental cell line. MiR-21 was overexpressed in the resistant cell line on microRNA microarray, which was subsequently validated with qRT-PCR. Using anti-microRNA inhibitors, we demonstrated that miR-21 attenuation reversed the drug resistant phenotype in both the resistant and parental cell lines. The inhibition of miR-21 induced apoptosis based on annexin V-FITC immunostaining. Using Western blot analysis, miR-21 knockdown enhanced the expression of tumor suppressor PDCD4, and attenuated apoptosis inhibitor c-IAP2. Using 101 specimens from advanced ovarian cancer patients enrolled in The Cancer Genome Atlas, we found that women with tumors that overexpressed miR-21 were associated with a shorter progression-free survival. Conclusion Our data suggest that miR-21 regulates drug resistance via apoptosis and cellular survival pathways. Targeting miR-21 may have clinical utility in the treatment of resistant ovarian cancer. |
| Databáze: | OpenAIRE |
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