A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation

Abstract mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axes for tumor initiation in early-onset breast cancer that is increasing drastically worldwide. To address this gap, we performed circular RNA (circRNA) microarrays and microRNA (miRNA) sequencing...

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Autores principales:	Nataly Naser Al Deen, Nadia Atallah Lanman, Shirisha Chittiboyina, Sophie Lelièvre, Rihab Nasr, Farah Nassar, Heinrich Zu Dohna, Mounir AbouHaidar, Rabih Talhouk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/894b1e32751742efa7e3f69f67100cba
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spelling	oai:doaj.org-article:894b1e32751742efa7e3f69f67100cba2021-12-02T13:57:36ZA risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation10.1038/s41598-021-82057-y2045-2322https://doaj.org/article/894b1e32751742efa7e3f69f67100cba2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82057-yhttps://doaj.org/toc/2045-2322Abstract mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axes for tumor initiation in early-onset breast cancer that is increasing drastically worldwide. To address this gap, we performed circular RNA (circRNA) microarrays and microRNA (miRNA) sequencing on acini of HMT-3522 S1 (S1) breast epithelial risk-progression culture model in 3D and chose an early-stage population miRNome for a validation cohort. Nontumorigenic S1 cells form fully polarized epithelium while pretumorigenic counterparts silenced for gap junction Cx43 (Cx43-KO-S1) lose epithelial polarity, multilayer and mimic premalignant in vivo mammary epithelial morphology. Here, 121 circRNAs and 65 miRNAs were significantly dysregulated in response to Cx43 silencing in cultured epithelia and 15 miRNAs from the patient cohort were involved in epithelial polarity disruption. Focusing on the possible sponging activity of the validated circRNAs to their target miRNAs, we found all miRNAs to be highly enriched in cancer-related pathways and cross-compared their dysregulation to actual miRNA datasets from the cultured epithelia and the patient validation cohort. We present the involvement of gap junction in post-transcriptional axes and reveal Cx43/hsa_circ_0077755/miR-182 as a potential biomarker signature axis for heightened-risk of breast cancer initiation, and that its dysregulation patterns might predict prognosis along breast cancer initiation and progression.Nataly Naser Al DeenNadia Atallah LanmanShirisha ChittiboyinaSophie LelièvreRihab NasrFarah NassarHeinrich Zu DohnaMounir AbouHaidarRabih TalhoukNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nataly Naser Al Deen Nadia Atallah Lanman Shirisha Chittiboyina Sophie Lelièvre Rihab Nasr Farah Nassar Heinrich Zu Dohna Mounir AbouHaidar Rabih Talhouk A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation
description	Abstract mRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axes for tumor initiation in early-onset breast cancer that is increasing drastically worldwide. To address this gap, we performed circular RNA (circRNA) microarrays and microRNA (miRNA) sequencing on acini of HMT-3522 S1 (S1) breast epithelial risk-progression culture model in 3D and chose an early-stage population miRNome for a validation cohort. Nontumorigenic S1 cells form fully polarized epithelium while pretumorigenic counterparts silenced for gap junction Cx43 (Cx43-KO-S1) lose epithelial polarity, multilayer and mimic premalignant in vivo mammary epithelial morphology. Here, 121 circRNAs and 65 miRNAs were significantly dysregulated in response to Cx43 silencing in cultured epithelia and 15 miRNAs from the patient cohort were involved in epithelial polarity disruption. Focusing on the possible sponging activity of the validated circRNAs to their target miRNAs, we found all miRNAs to be highly enriched in cancer-related pathways and cross-compared their dysregulation to actual miRNA datasets from the cultured epithelia and the patient validation cohort. We present the involvement of gap junction in post-transcriptional axes and reveal Cx43/hsa_circ_0077755/miR-182 as a potential biomarker signature axis for heightened-risk of breast cancer initiation, and that its dysregulation patterns might predict prognosis along breast cancer initiation and progression.
format	article
author	Nataly Naser Al Deen Nadia Atallah Lanman Shirisha Chittiboyina Sophie Lelièvre Rihab Nasr Farah Nassar Heinrich Zu Dohna Mounir AbouHaidar Rabih Talhouk
author_facet	Nataly Naser Al Deen Nadia Atallah Lanman Shirisha Chittiboyina Sophie Lelièvre Rihab Nasr Farah Nassar Heinrich Zu Dohna Mounir AbouHaidar Rabih Talhouk
author_sort	Nataly Naser Al Deen
title	A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation
title_short	A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation
title_full	A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation
title_fullStr	A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation
title_full_unstemmed	A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation
title_sort	risk progression breast epithelial 3d culture model reveals cx43/hsa_circ_0077755/mir-182 as a biomarker axis for heightened risk of breast cancer initiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/894b1e32751742efa7e3f69f67100cba
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A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation

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