Cargando…
Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763669/ https://www.ncbi.nlm.nih.gov/pubmed/33322148 http://dx.doi.org/10.3390/metabo10120509 |
_version_ | 1783628073184264192 |
---|---|
author | Lucarelli, Giuseppe Ferro, Matteo Loizzo, Davide Bianchi, Cristina Terracciano, Daniela Cantiello, Francesco Bell, Lauren N. Battaglia, Stefano Porta, Camillo Gernone, Angela Perego, Roberto A. Maiorano, Eugenio de Cobelli, Ottavio Castellano, Giuseppe Vincenti, Leonardo Ditonno, Pasquale Battaglia, Michele |
author_facet | Lucarelli, Giuseppe Ferro, Matteo Loizzo, Davide Bianchi, Cristina Terracciano, Daniela Cantiello, Francesco Bell, Lauren N. Battaglia, Stefano Porta, Camillo Gernone, Angela Perego, Roberto A. Maiorano, Eugenio de Cobelli, Ottavio Castellano, Giuseppe Vincenti, Leonardo Ditonno, Pasquale Battaglia, Michele |
author_sort | Lucarelli, Giuseppe |
collection | PubMed |
description | Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance. |
format | Online Article Text |
id | pubmed-7763669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77636692020-12-27 Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma Lucarelli, Giuseppe Ferro, Matteo Loizzo, Davide Bianchi, Cristina Terracciano, Daniela Cantiello, Francesco Bell, Lauren N. Battaglia, Stefano Porta, Camillo Gernone, Angela Perego, Roberto A. Maiorano, Eugenio de Cobelli, Ottavio Castellano, Giuseppe Vincenti, Leonardo Ditonno, Pasquale Battaglia, Michele Metabolites Article Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance. MDPI 2020-12-13 /pmc/articles/PMC7763669/ /pubmed/33322148 http://dx.doi.org/10.3390/metabo10120509 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lucarelli, Giuseppe Ferro, Matteo Loizzo, Davide Bianchi, Cristina Terracciano, Daniela Cantiello, Francesco Bell, Lauren N. Battaglia, Stefano Porta, Camillo Gernone, Angela Perego, Roberto A. Maiorano, Eugenio de Cobelli, Ottavio Castellano, Giuseppe Vincenti, Leonardo Ditonno, Pasquale Battaglia, Michele Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma |
title | Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma |
title_full | Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma |
title_fullStr | Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma |
title_full_unstemmed | Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma |
title_short | Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma |
title_sort | integration of lipidomics and transcriptomics reveals reprogramming of the lipid metabolism and composition in clear cell renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763669/ https://www.ncbi.nlm.nih.gov/pubmed/33322148 http://dx.doi.org/10.3390/metabo10120509 |
work_keys_str_mv | AT lucarelligiuseppe integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT ferromatteo integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT loizzodavide integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT bianchicristina integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT terraccianodaniela integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT cantiellofrancesco integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT belllaurenn integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT battagliastefano integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT portacamillo integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT gernoneangela integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT peregorobertoa integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT maioranoeugenio integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT decobelliottavio integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT castellanogiuseppe integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT vincentileonardo integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT ditonnopasquale integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma AT battagliamichele integrationoflipidomicsandtranscriptomicsrevealsreprogrammingofthelipidmetabolismandcompositioninclearcellrenalcellcarcinoma |