Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma
Renal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In th...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-07-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317707372 |
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| author | Kelly Gaudelot Jean-Baptiste Gibier Nicolas Pottier Brigitte Hémon Isabelle Van Seuningen François Glowacki Xavier Leroy Christelle Cauffiez Viviane Gnemmi Sébastien Aubert Michaël Perrais |
| author_facet | Kelly Gaudelot Jean-Baptiste Gibier Nicolas Pottier Brigitte Hémon Isabelle Van Seuningen François Glowacki Xavier Leroy Christelle Cauffiez Viviane Gnemmi Sébastien Aubert Michaël Perrais |
| author_sort | Kelly Gaudelot |
| collection | DOAJ |
| description | Renal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In this study, we focused our attention on miR-21, a well described oncomiR commonly upregulated in cancer. Using a cohort of 99 primary renal cell carcinoma samples, we showed that miR-21 expression in cancer tissues was higher than in adjacent non-tumor tissues whereas no significant difference was observed with stages, grades, and metastatic outcome. In vitro, miR-21 was also overexpressed in renal carcinoma cell lines compared to HK-2 human proximal tubule epithelial cell line. Moreover, using Boyden chambers and western blot techniques, we also showed that miR-21 overexpression increased migratory, invasive, proliferative, and anti-apoptotic signaling pathways whereas opposite results were observed using an anti-miR-21-based silencing strategy. Finally, we assessed the role of miR-21 in mediating renal cell carcinoma chemoresistance and further showed that miR-21 silencing significantly (1) increased chemosensitivity of paclitaxel, 5-fluorouracil, oxaliplatin, and dovitinib; (2) decreased expression of multi-drug resistance genes; and (4) increased SLC22A1/OCT1, SLC22A2/OCT2, and SLC31A1/CTR1 platinum influx transporter expression. In conclusion, our results showed that miR-21 is a key actor of renal cancer progression and plays an important role in the resistance to chemotherapeutic drugs. In renal cell carcinoma, targeting miR-21 is a potential new therapeutic strategy to improve chemotherapy efficacy and consequently patient outcome. |
| format | Article |
| id | doaj-art-6d8f402c6b994e3da4be2a77a2b99ac2 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-6d8f402c6b994e3da4be2a77a2b99ac22025-08-20T03:33:39ZengSAGE PublishingTumor Biology1423-03802017-07-013910.1177/1010428317707372Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinomaKelly Gaudelot0Jean-Baptiste Gibier1Nicolas Pottier2Brigitte Hémon3Isabelle Van Seuningen4François Glowacki5Xavier Leroy6Christelle Cauffiez7Viviane Gnemmi8Sébastien Aubert9Michaël Perrais10Université de Lille, Inserm, CHU Lille, UMR-S 1172, Team “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean-Pierre Aubert Research Center (JPARC), Lille, FranceCHU Lille, Pathology Institute, Centre de Biologie Pathologie, Rue Oscar Lambret, Lille, FranceCHU Lille, Department of Biochemistry and Molecular Biology, Centre de Biologie Pathologie, Rue Oscar Lambret, Lille, FranceUniversité de Lille, Inserm, CHU Lille, UMR-S 1172, Team “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean-Pierre Aubert Research Center (JPARC), Lille, FranceUniversité de Lille, Inserm, CHU Lille, UMR-S 1172, Team “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean-Pierre Aubert Research Center (JPARC), Lille, FranceCHU Lille, Department of Nephrology, Hôpital Huriez, Rue Michel Polonovski, Lille, FranceCHU Lille, Pathology Institute, Centre de Biologie Pathologie, Rue Oscar Lambret, Lille, FranceEA4483, Université de Lille, Faculté de Médecine, Pôle Recherche, Place de Verdun, Lille, FranceCHU Lille, Pathology Institute, Centre de Biologie Pathologie, Rue Oscar Lambret, Lille, FranceCHU Lille, Pathology Institute, Centre de Biologie Pathologie, Rue Oscar Lambret, Lille, FranceUniversité de Lille, Inserm, CHU Lille, UMR-S 1172, Team “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean-Pierre Aubert Research Center (JPARC), Lille, FranceRenal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In this study, we focused our attention on miR-21, a well described oncomiR commonly upregulated in cancer. Using a cohort of 99 primary renal cell carcinoma samples, we showed that miR-21 expression in cancer tissues was higher than in adjacent non-tumor tissues whereas no significant difference was observed with stages, grades, and metastatic outcome. In vitro, miR-21 was also overexpressed in renal carcinoma cell lines compared to HK-2 human proximal tubule epithelial cell line. Moreover, using Boyden chambers and western blot techniques, we also showed that miR-21 overexpression increased migratory, invasive, proliferative, and anti-apoptotic signaling pathways whereas opposite results were observed using an anti-miR-21-based silencing strategy. Finally, we assessed the role of miR-21 in mediating renal cell carcinoma chemoresistance and further showed that miR-21 silencing significantly (1) increased chemosensitivity of paclitaxel, 5-fluorouracil, oxaliplatin, and dovitinib; (2) decreased expression of multi-drug resistance genes; and (4) increased SLC22A1/OCT1, SLC22A2/OCT2, and SLC31A1/CTR1 platinum influx transporter expression. In conclusion, our results showed that miR-21 is a key actor of renal cancer progression and plays an important role in the resistance to chemotherapeutic drugs. In renal cell carcinoma, targeting miR-21 is a potential new therapeutic strategy to improve chemotherapy efficacy and consequently patient outcome.https://doi.org/10.1177/1010428317707372 |
| spellingShingle | Kelly Gaudelot Jean-Baptiste Gibier Nicolas Pottier Brigitte Hémon Isabelle Van Seuningen François Glowacki Xavier Leroy Christelle Cauffiez Viviane Gnemmi Sébastien Aubert Michaël Perrais Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma Tumor Biology |
| title | Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma |
| title_full | Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma |
| title_fullStr | Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma |
| title_full_unstemmed | Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma |
| title_short | Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma |
| title_sort | targeting mir 21 decreases expression of multi drug resistant genes and promotes chemosensitivity of renal carcinoma |
| url | https://doi.org/10.1177/1010428317707372 |
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