Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemic...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/830 |
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| author | Mariela Araya Francisca Sepúlveda Jaime Villegas Luis Alarcón Luis O. Burzio Verónica A. Burzio Vincenzo Borgna |
| author_facet | Mariela Araya Francisca Sepúlveda Jaime Villegas Luis Alarcón Luis O. Burzio Verónica A. Burzio Vincenzo Borgna |
| author_sort | Mariela Araya |
| collection | DOAJ |
| description | Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients. |
| first_indexed | 2024-03-07T22:38:42Z |
| format | Article |
| id | doaj.art-7848827377874c128790575bd1bc99b8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:38:42Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7848827377874c128790575bd1bc99b82024-02-23T15:11:22ZengMDPI AGCancers2072-66942024-02-0116483010.3390/cancers16040830Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse ModelMariela Araya0Francisca Sepúlveda1Jaime Villegas2Luis Alarcón3Luis O. Burzio4Verónica A. Burzio5Vincenzo Borgna6Centro Cientifico & Tecnologico de Excelencia Ciencia & Vida, Santiago 8580702, ChileCenter for Regenerative Medicine, Faculty of Clinical Medicine, Clínica Alemana, Universidad del Desarrollo, Santiago 7610615, ChileSchool of Veterinary Medicine, Faculty of Life Sciences, Universidad Andrés Bello, Santiago 8370251, ChileUrology Service, Hospital Barros Luco-Trudeau, Santiago 8900085, ChileDepartment of Biological Sciences, Faculty of Life Sciences, Universidad Andrés Bello, Santiago 8370251, ChileDepartment of Biological Sciences, Faculty of Life Sciences, Universidad Andrés Bello, Santiago 8370251, ChileCentro Cientifico & Tecnologico de Excelencia Ciencia & Vida, Santiago 8580702, ChileClear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.https://www.mdpi.com/2072-6694/16/4/830clear cell renal cell carcinomanon-coding RNAcancer therapyorthotopic mouse renal modelpatient-derived primary cultures |
| spellingShingle | Mariela Araya Francisca Sepúlveda Jaime Villegas Luis Alarcón Luis O. Burzio Verónica A. Burzio Vincenzo Borgna Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model Cancers clear cell renal cell carcinoma non-coding RNA cancer therapy orthotopic mouse renal model patient-derived primary cultures |
| title | Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model |
| title_full | Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model |
| title_fullStr | Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model |
| title_full_unstemmed | Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model |
| title_short | Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model |
| title_sort | knockdown of antisense noncoding mitochondrial rna reduces tumorigenicity of patient derived clear cell renal carcinoma cells in an orthotopic xenograft mouse model |
| topic | clear cell renal cell carcinoma non-coding RNA cancer therapy orthotopic mouse renal model patient-derived primary cultures |
| url | https://www.mdpi.com/2072-6694/16/4/830 |
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