miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
Abstract Background Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The pur...
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01623-y |
| _version_ | 1831714297635405824 |
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| author | Xiaotang Yu Xinchen Zhang Guang Wang Bo Wang Yanfang Ding Jinyao Zhao Hanlin Liu Shiying Cui |
| author_facet | Xiaotang Yu Xinchen Zhang Guang Wang Bo Wang Yanfang Ding Jinyao Zhao Hanlin Liu Shiying Cui |
| author_sort | Xiaotang Yu |
| collection | DOAJ |
| description | Abstract Background Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. Methods MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. Results miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. Conclusion miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction. |
| first_indexed | 2024-12-20T23:55:33Z |
| format | Article |
| id | doaj.art-c99bc4c32ad342788d1b80d1902d0730 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-20T23:55:33Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-c99bc4c32ad342788d1b80d1902d07302022-12-21T19:22:43ZengBMCCancer Cell International1475-28672020-11-0120111610.1186/s12935-020-01623-ymiR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancerXiaotang Yu0Xinchen Zhang1Guang Wang2Bo Wang3Yanfang Ding4Jinyao Zhao5Hanlin Liu6Shiying Cui7Department of Pathology and Forensic Medicine, College of Basic Medicine Sciences, Dalian Medical UniversityDepartment of Histology and Embryology, Dalian Medical University, College of Basic Medicine SciencesDepartment of Histology and Embryology, Dalian Medical University, College of Basic Medicine SciencesDepartment of Pathology and Forensic Medicine, College of Basic Medicine Sciences, Dalian Medical UniversityDepartment of Histology and Embryology, Dalian Medical University, College of Basic Medicine SciencesCancer Stem Cell Institute, Dalian Medical UniversityDepartment of Histology and Embryology, Dalian Medical University, College of Basic Medicine SciencesDepartment of Histology and Embryology, Dalian Medical University, College of Basic Medicine SciencesAbstract Background Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. Methods MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. Results miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. Conclusion miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.http://link.springer.com/article/10.1186/s12935-020-01623-yEpithelial ovarian cancerPlatinumChemoresistancemiR-206 |
| spellingShingle | Xiaotang Yu Xinchen Zhang Guang Wang Bo Wang Yanfang Ding Jinyao Zhao Hanlin Liu Shiying Cui miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer Cancer Cell International Epithelial ovarian cancer Platinum Chemoresistance miR-206 |
| title | miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer |
| title_full | miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer |
| title_fullStr | miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer |
| title_full_unstemmed | miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer |
| title_short | miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer |
| title_sort | mir 206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer |
| topic | Epithelial ovarian cancer Platinum Chemoresistance miR-206 |
| url | http://link.springer.com/article/10.1186/s12935-020-01623-y |
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