Enhancement of Breast Cancer Cell Aggressiveness by lncRNA H19 and its Mir-675 Derivative: Insight into Shared and Different Actions

Breast cancer is a major public health problem and the leading world cause of women death by cancer. Both the recurrence and mortality of breast cancer are mainly caused by the formation of metastasis. The long non-coding RNAH19, the precursor of miR-675, is involved in breast cancer development. The aim of this work was to determine the implication but, also, the relative contribution ofH19and miR-675 to the enhancement of breast cancer metastatic potential. We showed that bothH19and miR-675 increase the invasive capacities of breast cancer cells in xenografted transgenic zebrafish models. In vitro,H19and miR-675 enhance the cell migration and invasion, as well as colony formation.H19seems to induce the epithelial-to-mesenchymal transition (EMT), with a decreased expression of epithelial markers and an increased expression of mesenchymal markers. Interestingly, miR-675 simultaneously increases the expression of both epithelial and mesenchymal markers, suggesting the induction of a hybrid phenotype or mesenchymal-to-epithelial transition (MET). Finally, we demonstrated for the first time that miR-675, like its precursorH19,increases the stemness properties of breast cancer cells. Altogether, our data suggest thatH19and miR-675 could enhance the aggressiveness of breast cancer cells through both common and different mechanisms.