Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo

Abstract Regulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may direct...

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Autores principales:	Siamak Salehi, Oliver D. Tavabie, Augusto Villanueva, Julie Watson, David Darling, Alberto Quaglia, Farzin Farzaneh, Varuna R. Aluvihare
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/388244267b7e431ea2ab847dde7cac1e
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spelling	oai:doaj.org-article:388244267b7e431ea2ab847dde7cac1e2021-12-02T15:45:26ZRegeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo10.1038/s41598-021-90009-92045-2322https://doaj.org/article/388244267b7e431ea2ab847dde7cac1e2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90009-9https://doaj.org/toc/2045-2322Abstract Regulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.Siamak SalehiOliver D. TavabieAugusto VillanuevaJulie WatsonDavid DarlingAlberto QuagliaFarzin FarzanehVaruna R. AluvihareNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Siamak Salehi Oliver D. Tavabie Augusto Villanueva Julie Watson David Darling Alberto Quaglia Farzin Farzaneh Varuna R. Aluvihare Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
description	Abstract Regulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.
format	article
author	Siamak Salehi Oliver D. Tavabie Augusto Villanueva Julie Watson David Darling Alberto Quaglia Farzin Farzaneh Varuna R. Aluvihare
author_facet	Siamak Salehi Oliver D. Tavabie Augusto Villanueva Julie Watson David Darling Alberto Quaglia Farzin Farzaneh Varuna R. Aluvihare
author_sort	Siamak Salehi
title	Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
title_short	Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
title_full	Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
title_fullStr	Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
title_full_unstemmed	Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
title_sort	regeneration linked mirna modify tumor phenotype and can enforce multi-lineage growth arrest in vivo
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/388244267b7e431ea2ab847dde7cac1e
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Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo

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