Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects
The identification of miRNAs’ targets and associated regulatory networks might allow the definition of new strategies using drugs whose association mimics a given miRNA’s effects. Based on this assumption we devised a multi-omics approach to precisely characterize miRNAs’ effects. We combined miR-49...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/3970 |
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| author | Matthieu Meryet-Figuiere Mégane Vernon Mamy Andrianteranagna Bernard Lambert Célia Brochen Jean-Paul Issartel Audrey Guttin Pascal Gauduchon Emilie Brotin Florent Dingli Damarys Loew Nicolas Vigneron Anaïs Wambecke Edwige Abeilard Emmanuel Barillot Laurent Poulain Loredana Martignetti Christophe Denoyelle |
| author_facet | Matthieu Meryet-Figuiere Mégane Vernon Mamy Andrianteranagna Bernard Lambert Célia Brochen Jean-Paul Issartel Audrey Guttin Pascal Gauduchon Emilie Brotin Florent Dingli Damarys Loew Nicolas Vigneron Anaïs Wambecke Edwige Abeilard Emmanuel Barillot Laurent Poulain Loredana Martignetti Christophe Denoyelle |
| author_sort | Matthieu Meryet-Figuiere |
| collection | DOAJ |
| description | The identification of miRNAs’ targets and associated regulatory networks might allow the definition of new strategies using drugs whose association mimics a given miRNA’s effects. Based on this assumption we devised a multi-omics approach to precisely characterize miRNAs’ effects. We combined miR-491-5p target affinity purification, RNA microarray, and mass spectrometry to perform an integrated analysis in ovarian cancer cell lines. We thus constructed an interaction network that highlighted highly connected hubs being either direct or indirect targets of miR-491-5p effects: the already known EGFR and BCL2L1 but also EP300, CTNNB1 and several small-GTPases. By using different combinations of specific inhibitors of these hubs, we could greatly enhance their respective cytotoxicity and mimic the miR-491-5p-induced phenotype. Our methodology thus constitutes an interesting strategy to comprehensively study the effects of a given miRNA. Moreover, we identified targets for which pharmacological inhibitors are already available for a clinical use or in clinical trials. This study might thus enable innovative therapeutic options for ovarian cancer, which remains the leading cause of death from gynecological malignancies in developed countries. |
| first_indexed | 2024-03-10T08:57:08Z |
| format | Article |
| id | doaj.art-11e926ab40b840498bae9039620f1c7c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:57:08Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-11e926ab40b840498bae9039620f1c7c2023-11-22T07:01:49ZengMDPI AGCancers2072-66942021-08-011316397010.3390/cancers13163970Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p EffectsMatthieu Meryet-Figuiere0Mégane Vernon1Mamy Andrianteranagna2Bernard Lambert3Célia Brochen4Jean-Paul Issartel5Audrey Guttin6Pascal Gauduchon7Emilie Brotin8Florent Dingli9Damarys Loew10Nicolas Vigneron11Anaïs Wambecke12Edwige Abeilard13Emmanuel Barillot14Laurent Poulain15Loredana Martignetti16Christophe Denoyelle17Normandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceINSERM U1216, Core Facility of Clinical Transcriptomics, Neurosciences Institute, 38000 Grenoble, FranceINSERM U1216, Core Facility of Clinical Transcriptomics, Neurosciences Institute, 38000 Grenoble, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceMass Spectrometry and Proteomics Facility (LSMP), Institut Curie, PSL Research University, 75000 Paris, FranceMass Spectrometry and Proteomics Facility (LSMP), Institut Curie, PSL Research University, 75000 Paris, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceInstitut Curie, PSL Research University, 75005 Paris, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceInstitut Curie, PSL Research University, 75005 Paris, FranceNormandie University, UNICAEN, Inserm U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), 14000 Caen, FranceThe identification of miRNAs’ targets and associated regulatory networks might allow the definition of new strategies using drugs whose association mimics a given miRNA’s effects. Based on this assumption we devised a multi-omics approach to precisely characterize miRNAs’ effects. We combined miR-491-5p target affinity purification, RNA microarray, and mass spectrometry to perform an integrated analysis in ovarian cancer cell lines. We thus constructed an interaction network that highlighted highly connected hubs being either direct or indirect targets of miR-491-5p effects: the already known EGFR and BCL2L1 but also EP300, CTNNB1 and several small-GTPases. By using different combinations of specific inhibitors of these hubs, we could greatly enhance their respective cytotoxicity and mimic the miR-491-5p-induced phenotype. Our methodology thus constitutes an interesting strategy to comprehensively study the effects of a given miRNA. Moreover, we identified targets for which pharmacological inhibitors are already available for a clinical use or in clinical trials. This study might thus enable innovative therapeutic options for ovarian cancer, which remains the leading cause of death from gynecological malignancies in developed countries.https://www.mdpi.com/2072-6694/13/16/3970networkmulti-omicsmiRNAmiR-491-5povarian cancer |
| spellingShingle | Matthieu Meryet-Figuiere Mégane Vernon Mamy Andrianteranagna Bernard Lambert Célia Brochen Jean-Paul Issartel Audrey Guttin Pascal Gauduchon Emilie Brotin Florent Dingli Damarys Loew Nicolas Vigneron Anaïs Wambecke Edwige Abeilard Emmanuel Barillot Laurent Poulain Loredana Martignetti Christophe Denoyelle Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects Cancers network multi-omics miRNA miR-491-5p ovarian cancer |
| title | Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects |
| title_full | Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects |
| title_fullStr | Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects |
| title_full_unstemmed | Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects |
| title_short | Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects |
| title_sort | network based integration of multi omics data identifies the determinants of mir 491 5p effects |
| topic | network multi-omics miRNA miR-491-5p ovarian cancer |
| url | https://www.mdpi.com/2072-6694/13/16/3970 |
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