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
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Acceso en línea:https://doaj.org/article/1a2eae02a57247598cac1bd7169768db
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Sumario: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.