Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)

Abstract Hepatic cancer stem cells (HCSCs) are considered as main players for the hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance and recurrence. There is a growing evidence supporting the down-regulated miRNAs in HCSCs as key suppressors for the stemness traits, but still mor...

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Autores principales:	Rania Hassan Mohamed, Nourhan Abu-Shahba, Marwa Mahmoud, Ahmed M. H. Abdelfattah, Wael Zakaria, Mahmoud ElHefnawi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6644d1381e754e7fa6ea5a758c967797
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spelling	oai:doaj.org-article:6644d1381e754e7fa6ea5a758c9677972021-12-02T15:08:47ZCo-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)10.1038/s41598-019-41978-52045-2322https://doaj.org/article/6644d1381e754e7fa6ea5a758c9677972019-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-41978-5https://doaj.org/toc/2045-2322Abstract Hepatic cancer stem cells (HCSCs) are considered as main players for the hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance and recurrence. There is a growing evidence supporting the down-regulated miRNAs in HCSCs as key suppressors for the stemness traits, but still more details are vague about how these miRNAs modulate the HCC development. To uncover some of these miRNA regulatory aspects in HCSC, we compiled 15 down-regulated miRNA and their validated and predicted up-regulated targets in HCSC. The targets were enriched for several cancer cell stemness hallmarks and CSC pre-metastatic niche, which support these miRNAs role in suppression of HCSCs neoplastic transformation. Further, we constructed miRNA-Transcription factor (TF) regulatory networks, which provided new insights on the role of the proposed miRNA-TF co-regulation in the cancer stemness axis and its cross talk with the surrounding microenvironment. Our analysis revealed HCSC important hubs as candidate regulators for targeting hepatic cancer stemness such as, miR-148a, miR-214, E2F family, MYC and SLC7A5. Finally, we proposed a possible model for miRNA and TF co-regulation of HCSC signaling pathways. Our study identified an HCSC signature and set bridges between the reported results to give guide for future validation of HCC therapeutic strategies avoiding drug resistance.Rania Hassan MohamedNourhan Abu-ShahbaMarwa MahmoudAhmed M. H. AbdelfattahWael ZakariaMahmoud ElHefnawiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rania Hassan Mohamed Nourhan Abu-Shahba Marwa Mahmoud Ahmed M. H. Abdelfattah Wael Zakaria Mahmoud ElHefnawi Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)
description	Abstract Hepatic cancer stem cells (HCSCs) are considered as main players for the hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance and recurrence. There is a growing evidence supporting the down-regulated miRNAs in HCSCs as key suppressors for the stemness traits, but still more details are vague about how these miRNAs modulate the HCC development. To uncover some of these miRNA regulatory aspects in HCSC, we compiled 15 down-regulated miRNA and their validated and predicted up-regulated targets in HCSC. The targets were enriched for several cancer cell stemness hallmarks and CSC pre-metastatic niche, which support these miRNAs role in suppression of HCSCs neoplastic transformation. Further, we constructed miRNA-Transcription factor (TF) regulatory networks, which provided new insights on the role of the proposed miRNA-TF co-regulation in the cancer stemness axis and its cross talk with the surrounding microenvironment. Our analysis revealed HCSC important hubs as candidate regulators for targeting hepatic cancer stemness such as, miR-148a, miR-214, E2F family, MYC and SLC7A5. Finally, we proposed a possible model for miRNA and TF co-regulation of HCSC signaling pathways. Our study identified an HCSC signature and set bridges between the reported results to give guide for future validation of HCC therapeutic strategies avoiding drug resistance.
format	article
author	Rania Hassan Mohamed Nourhan Abu-Shahba Marwa Mahmoud Ahmed M. H. Abdelfattah Wael Zakaria Mahmoud ElHefnawi
author_facet	Rania Hassan Mohamed Nourhan Abu-Shahba Marwa Mahmoud Ahmed M. H. Abdelfattah Wael Zakaria Mahmoud ElHefnawi
author_sort	Rania Hassan Mohamed
title	Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)
title_short	Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)
title_full	Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)
title_fullStr	Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)
title_full_unstemmed	Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)
title_sort	co-regulatory network of oncosuppressor mirnas and transcription factors for pathology of human hepatic cancer stem cells (hcsc)
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/6644d1381e754e7fa6ea5a758c967797
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Co-regulatory Network of Oncosuppressor miRNAs and Transcription Factors for Pathology of Human Hepatic Cancer Stem Cells (HCSC)

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