A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells

Circular RNAs are regulatory molecules involved in numerous cellular processes and may be involved in tumour growth and diffusion. Here, we define the expression of 15 selected circular RNAs, which may control the process of epithelial-to-mesenchymal transition, using a panel of 18 breast cancer cel...

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Autores principales:	Mami Kurosaki, Mineko Terao, Dawei Liu, Adriana Zanetti, Luca Guarrera, Marco Bolis, Maurizio Gianni’, Gabriela Paroni, Gregory J. Goodall, Enrico Garattini
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	circular RNAs breast cancer RNA sequencing differentiation epithelial-to-mesenchymal transition (EMT) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1a2eae02a57247598cac1bd7169768db
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spelling	oai:doaj.org-article:1a2eae02a57247598cac1bd7169768db2021-11-11T15:28:20ZA <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells10.3390/cancers132153252072-6694https://doaj.org/article/1a2eae02a57247598cac1bd7169768db2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5325https://doaj.org/toc/2072-6694Circular RNAs are regulatory molecules involved in numerous cellular processes and may be involved in tumour growth and diffusion. Here, we define the expression of 15 selected circular RNAs, which may control the process of epithelial-to-mesenchymal transition, using a panel of 18 breast cancer cell lines recapitulating the heterogeneity of these tumours and consisting of three groups according to the mesenchymal/epithelial phenotype. A circular RNA from the <i>DOCK1</i> gene (<i>hsa_circ_0020397</i>) shows low/undetectable levels in triple-negative mesenchymal cell lines, while its content is high in epithelial cell lines, independent of estrogen receptor or HER2 positivity. RNA-sequencing experiments performed on the triple-negative/mesenchymal <i>MDA-MB-231</i> and <i>MDA-MB-157</i> cell lines engineered to overexpress <i>hsa_circ_0020397</i> demonstrate that the circRNA influences the expression of 110 common genes. Pathway analysis of these genes indicates that overexpression of the circular RNA differentiates the two mesenchymal cell lines along the epithelial pathway and increases cell-to-cell adhesion. This is accompanied by growth inhibition and a reduction in the random/directional motility of the cell lines. The upregulated <i>AGR2</i>, <i>ENPP1</i>, and <i>PPP1R9A</i> genes as well as the downregulated <i>APOE</i>, <i>AQP3</i>, <i>CD99L2</i>, and <i>IGFBP4</i> genes show an opposite regulation by <i>hsa_circ_0020397</i> silencing in luminal <i>CAMA1</i> cells. The results provide novel insights into the role played by specific circular RNAs in the generation/progression of breast cancer.Mami KurosakiMineko TeraoDawei LiuAdriana ZanettiLuca GuarreraMarco BolisMaurizio Gianni’Gabriela ParoniGregory J. GoodallEnrico GarattiniMDPI AGarticlecircular RNAsbreast cancerRNA sequencingdifferentiationepithelial-to-mesenchymal transition (EMT)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5325, p 5325 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circular RNAs breast cancer RNA sequencing differentiation epithelial-to-mesenchymal transition (EMT) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	circular RNAs breast cancer RNA sequencing differentiation epithelial-to-mesenchymal transition (EMT) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mami Kurosaki Mineko Terao Dawei Liu Adriana Zanetti Luca Guarrera Marco Bolis Maurizio Gianni’ Gabriela Paroni Gregory J. Goodall Enrico Garattini A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
description	Circular RNAs are regulatory molecules involved in numerous cellular processes and may be involved in tumour growth and diffusion. Here, we define the expression of 15 selected circular RNAs, which may control the process of epithelial-to-mesenchymal transition, using a panel of 18 breast cancer cell lines recapitulating the heterogeneity of these tumours and consisting of three groups according to the mesenchymal/epithelial phenotype. A circular RNA from the <i>DOCK1</i> gene (<i>hsa_circ_0020397</i>) shows low/undetectable levels in triple-negative mesenchymal cell lines, while its content is high in epithelial cell lines, independent of estrogen receptor or HER2 positivity. RNA-sequencing experiments performed on the triple-negative/mesenchymal <i>MDA-MB-231</i> and <i>MDA-MB-157</i> cell lines engineered to overexpress <i>hsa_circ_0020397</i> demonstrate that the circRNA influences the expression of 110 common genes. Pathway analysis of these genes indicates that overexpression of the circular RNA differentiates the two mesenchymal cell lines along the epithelial pathway and increases cell-to-cell adhesion. This is accompanied by growth inhibition and a reduction in the random/directional motility of the cell lines. The upregulated <i>AGR2</i>, <i>ENPP1</i>, and <i>PPP1R9A</i> genes as well as the downregulated <i>APOE</i>, <i>AQP3</i>, <i>CD99L2</i>, and <i>IGFBP4</i> genes show an opposite regulation by <i>hsa_circ_0020397</i> silencing in luminal <i>CAMA1</i> cells. The results provide novel insights into the role played by specific circular RNAs in the generation/progression of breast cancer.
format	article
author	Mami Kurosaki Mineko Terao Dawei Liu Adriana Zanetti Luca Guarrera Marco Bolis Maurizio Gianni’ Gabriela Paroni Gregory J. Goodall Enrico Garattini
author_facet	Mami Kurosaki Mineko Terao Dawei Liu Adriana Zanetti Luca Guarrera Marco Bolis Maurizio Gianni’ Gabriela Paroni Gregory J. Goodall Enrico Garattini
author_sort	Mami Kurosaki
title	A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
title_short	A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
title_full	A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
title_fullStr	A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
title_full_unstemmed	A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
title_sort	<i>dock1</i> gene-derived circular rna is highly expressed in luminal mammary tumours and is involved in the epithelial differentiation, growth, and motility of breast cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1a2eae02a57247598cac1bd7169768db
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A <i>DOCK1</i> Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells

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