DOCK1 gene derived hsa_circ_0020397 RNA is over-expressed in luminal mammary tumors and it is involved in the epithelial differentiation, growth and motility of the neoplastic cell

Circular-RNAs are an emerging group of regulatory molecules involved in the control of numerous cellular processes and may play a role in the growth and diffusion of various types of tumors. In the present study, we define the expression of 15 selected circular-RNAs, which may be involved in the process of epithelial-to-mesenchymal-transition, using a panel of 18 breast cancer cell-lines recapitulating the heterogeneity of the tumor and consisting of three distinct groups according to the mesenchymal/epithelial phenotype. The circular RNA deriving from the DOCK1 gene (hsa_circ_0020397) is characterized by the most interesting expression profile, as it is undetectable in triple-negative mesenchymal cell-lines, while it is easily measurable in epithelial cell-lines independent of their positivity to estrogen receptor or the HER2 membrane receptor. Whole-genome RNA-sequencing experiments performed on the triple-negative/mesenchymal MDA-MB-231 and MDA-MB-157 cell-lines engineered to over-express hsa_circ_0020397 demonstrate that the circular-RNA controls the expression of 110 common genes. Pathway analysis of these genes indicate that over-expression of the circular-RNA differentiates the two mesenchymal cell-lines along the epithelial pathway and increase cell-to-cell adhesion. This is accompanied by a growth inhibitory effect and a reduction in the random/directional motility of the two cell-lines. The up-regulated AGR2, ENPP1 and PPP1R9A genes as well as the down-regulated APOE, AQP3, CD99L2 and IGFBP4 genes show an opposite regulation by circDOCK1 silencing in CAMA1 luminal cells.