MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression
During tumor progression, cancer cells rewire their metabolism to face their bioenergetic demands. In recent years, microRNAs (miRNAs) have emerged as regulatory elements that inhibit the translation and stability of crucial mRNAs, some of them causing direct metabolic alterations in cancer. In this...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.582396/full |
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| author | Erick Andrés Muciño-Olmos Erick Andrés Muciño-Olmos Aarón Vázquez-Jiménez Diana Elena López-Esparza Vilma Maldonado Mahara Valverde Osbaldo Resendis-Antonio Osbaldo Resendis-Antonio |
| author_facet | Erick Andrés Muciño-Olmos Erick Andrés Muciño-Olmos Aarón Vázquez-Jiménez Diana Elena López-Esparza Vilma Maldonado Mahara Valverde Osbaldo Resendis-Antonio Osbaldo Resendis-Antonio |
| author_sort | Erick Andrés Muciño-Olmos |
| collection | DOAJ |
| description | During tumor progression, cancer cells rewire their metabolism to face their bioenergetic demands. In recent years, microRNAs (miRNAs) have emerged as regulatory elements that inhibit the translation and stability of crucial mRNAs, some of them causing direct metabolic alterations in cancer. In this study, we investigated the relationship between miRNAs and their targets mRNAs that control metabolism, and how this fine-tuned regulation is diversified depending on the tumor stage. To do so, we implemented a paired analysis of RNA-seq and small RNA-seq in a breast cancer cell line (MCF7). The cell line was cultured in multicellular tumor spheroid (MCTS) and monoculture conditions. For MCTS, we selected two-time points during their development to recapitulate a proliferative and quiescent stage and contrast their miRNA and mRNA expression patterns associated with metabolism. As a result, we identified a set of new direct putative regulatory interactions between miRNAs and metabolic mRNAs representative for proliferative and quiescent stages. Notably, our study allows us to suggest that miR-3143 regulates the carbon metabolism by targeting hexokinase-2. Also, we found that the overexpression of several miRNAs could directly overturn the expression of mRNAs that control glycerophospholipid and N-Glycan metabolism. While this set of miRNAs downregulates their expression in the quiescent stage, the same set is upregulated in proliferative stages. This last finding suggests an additional metabolic switch of the above mentioned metabolic pathways between the quiescent and proliferative stages. Our results contribute to a better understanding of how miRNAs modulate the metabolic landscape in breast cancer MCTS, which eventually will help to design new strategies to mitigate cancer phenotype. |
| first_indexed | 2024-12-20T01:08:30Z |
| format | Article |
| id | doaj.art-79a4aac4de52481fb0c51d8d972d2cd3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T01:08:30Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-79a4aac4de52481fb0c51d8d972d2cd32022-12-21T19:58:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.582396582396MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids ProgressionErick Andrés Muciño-Olmos0Erick Andrés Muciño-Olmos1Aarón Vázquez-Jiménez2Diana Elena López-Esparza3Vilma Maldonado4Mahara Valverde5Osbaldo Resendis-Antonio6Osbaldo Resendis-Antonio7Human Systems Biology Lab, National Institute of Genomic Medicine, Mexico City, MexicoPhD Program in Biomedical Sciences, UNAM, Mexico City, MexicoHuman Systems Biology Lab, National Institute of Genomic Medicine, Mexico City, MexicoUnidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”—Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, MexicoEpigenetic Laboratory, Instituto Nacional de Medicina Genómica, Ciudad de México, MexicoDepartment of Genomic Medicine and Environmental Toxicology, Institute for Biomedical Research, National Autonomous University of Mexico, Mexico City, MexicoHuman Systems Biology Lab, National Institute of Genomic Medicine, Mexico City, MexicoCoordinación de La Investigación Científica -Red de Apoyo a La Investigación, UNAM, Mexico City, MexicoDuring tumor progression, cancer cells rewire their metabolism to face their bioenergetic demands. In recent years, microRNAs (miRNAs) have emerged as regulatory elements that inhibit the translation and stability of crucial mRNAs, some of them causing direct metabolic alterations in cancer. In this study, we investigated the relationship between miRNAs and their targets mRNAs that control metabolism, and how this fine-tuned regulation is diversified depending on the tumor stage. To do so, we implemented a paired analysis of RNA-seq and small RNA-seq in a breast cancer cell line (MCF7). The cell line was cultured in multicellular tumor spheroid (MCTS) and monoculture conditions. For MCTS, we selected two-time points during their development to recapitulate a proliferative and quiescent stage and contrast their miRNA and mRNA expression patterns associated with metabolism. As a result, we identified a set of new direct putative regulatory interactions between miRNAs and metabolic mRNAs representative for proliferative and quiescent stages. Notably, our study allows us to suggest that miR-3143 regulates the carbon metabolism by targeting hexokinase-2. Also, we found that the overexpression of several miRNAs could directly overturn the expression of mRNAs that control glycerophospholipid and N-Glycan metabolism. While this set of miRNAs downregulates their expression in the quiescent stage, the same set is upregulated in proliferative stages. This last finding suggests an additional metabolic switch of the above mentioned metabolic pathways between the quiescent and proliferative stages. Our results contribute to a better understanding of how miRNAs modulate the metabolic landscape in breast cancer MCTS, which eventually will help to design new strategies to mitigate cancer phenotype.https://www.frontiersin.org/articles/10.3389/fonc.2020.582396/fullcancer metabolismmiRNA-mRNA interactionmulticellular tumor spheroidsbioinformaticsmiRNA target prediction |
| spellingShingle | Erick Andrés Muciño-Olmos Erick Andrés Muciño-Olmos Aarón Vázquez-Jiménez Diana Elena López-Esparza Vilma Maldonado Mahara Valverde Osbaldo Resendis-Antonio Osbaldo Resendis-Antonio MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression Frontiers in Oncology cancer metabolism miRNA-mRNA interaction multicellular tumor spheroids bioinformatics miRNA target prediction |
| title | MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression |
| title_full | MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression |
| title_fullStr | MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression |
| title_full_unstemmed | MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression |
| title_short | MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression |
| title_sort | micrornas regulate metabolic phenotypes during multicellular tumor spheroids progression |
| topic | cancer metabolism miRNA-mRNA interaction multicellular tumor spheroids bioinformatics miRNA target prediction |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.582396/full |
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