Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9

Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involv...

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Autores principales:	Miriam Buttacavoli, Gianluca Di Cara, Elena Roz, Ida Pucci-Minafra, Salvatore Feo, Patrizia Cancemi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	matrix metalloproteinases gene expression colon cancer proteomics bioinformatics MMP2 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/fbdbf667fff548afb0643e9ff5307b0b
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spelling	oai:doaj.org-article:fbdbf667fff548afb0643e9ff5307b0b2021-11-25T17:56:10ZIntegrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP910.3390/ijms2222123891422-00671661-6596https://doaj.org/article/fbdbf667fff548afb0643e9ff5307b0b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12389https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in ECM remodeling and the processing of bioactive molecules. Increased MMP expression promotes the hallmarks of tumor progression, including angiogenesis, invasion, and metastasis, and is correlated with a shortened survival. Nevertheless, the collective role and the possible coordination of MMP members in CRC are poorly investigated. Here, we performed a multi-omics analysis of MMP expression in CRC using data mining and experimental investigations. Several databases were used to deeply mine different expressions between tumor and normal tissues, the genetic and epigenetic alterations, the prognostic value as well as the interrelationships with tumor immune-infiltrating cells (TIICs). A special focus was placed on to MMP2 and MMP9: their expression was correlated with immune markers and the interaction network of co-expressed genes disclosed their implication in epithelial to mesenchymal transition (EMT) and immune response. Finally, the activity levels of MMP2 and MMP9 in a cohort of colon cancer samples, including tissues and the corresponding sera, was also investigated by zymography. Our findings suggested that MMPs could have a high potency, as they are targeted in colon cancer, and might serve as novel biomarkers, especially for their involvement in the immune response. However, further studies are needed to explore the detailed biological functions and molecular mechanisms of MMPs in CRC, also in consideration of their expression and different regulation in several tissues.Miriam ButtacavoliGianluca Di CaraElena RozIda Pucci-MinafraSalvatore FeoPatrizia CancemiMDPI AGarticlematrix metalloproteinasesgene expressioncolon cancerproteomicsbioinformaticsMMP2Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12389, p 12389 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	matrix metalloproteinases gene expression colon cancer proteomics bioinformatics MMP2 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	matrix metalloproteinases gene expression colon cancer proteomics bioinformatics MMP2 Biology (General) QH301-705.5 Chemistry QD1-999 Miriam Buttacavoli Gianluca Di Cara Elena Roz Ida Pucci-Minafra Salvatore Feo Patrizia Cancemi Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9
description	Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in ECM remodeling and the processing of bioactive molecules. Increased MMP expression promotes the hallmarks of tumor progression, including angiogenesis, invasion, and metastasis, and is correlated with a shortened survival. Nevertheless, the collective role and the possible coordination of MMP members in CRC are poorly investigated. Here, we performed a multi-omics analysis of MMP expression in CRC using data mining and experimental investigations. Several databases were used to deeply mine different expressions between tumor and normal tissues, the genetic and epigenetic alterations, the prognostic value as well as the interrelationships with tumor immune-infiltrating cells (TIICs). A special focus was placed on to MMP2 and MMP9: their expression was correlated with immune markers and the interaction network of co-expressed genes disclosed their implication in epithelial to mesenchymal transition (EMT) and immune response. Finally, the activity levels of MMP2 and MMP9 in a cohort of colon cancer samples, including tissues and the corresponding sera, was also investigated by zymography. Our findings suggested that MMPs could have a high potency, as they are targeted in colon cancer, and might serve as novel biomarkers, especially for their involvement in the immune response. However, further studies are needed to explore the detailed biological functions and molecular mechanisms of MMPs in CRC, also in consideration of their expression and different regulation in several tissues.
format	article
author	Miriam Buttacavoli Gianluca Di Cara Elena Roz Ida Pucci-Minafra Salvatore Feo Patrizia Cancemi
author_facet	Miriam Buttacavoli Gianluca Di Cara Elena Roz Ida Pucci-Minafra Salvatore Feo Patrizia Cancemi
author_sort	Miriam Buttacavoli
title	Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9
title_short	Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9
title_full	Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9
title_fullStr	Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9
title_full_unstemmed	Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9
title_sort	integrated multi-omics investigations of metalloproteinases in colon cancer: focus on mmp2 and mmp9
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fbdbf667fff548afb0643e9ff5307b0b
work_keys_str_mv	AT miriambuttacavoli integratedmultiomicsinvestigationsofmetalloproteinasesincoloncancerfocusonmmp2andmmp9 AT gianlucadicara integratedmultiomicsinvestigationsofmetalloproteinasesincoloncancerfocusonmmp2andmmp9 AT elenaroz integratedmultiomicsinvestigationsofmetalloproteinasesincoloncancerfocusonmmp2andmmp9 AT idapucciminafra integratedmultiomicsinvestigationsofmetalloproteinasesincoloncancerfocusonmmp2andmmp9 AT salvatorefeo integratedmultiomicsinvestigationsofmetalloproteinasesincoloncancerfocusonmmp2andmmp9 AT patriziacancemi integratedmultiomicsinvestigationsofmetalloproteinasesincoloncancerfocusonmmp2andmmp9
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Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9

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