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 RNA H19, 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 of H19 and miR-675 to the enhancement of breast cancer metastatic potential. We showed that both H19 and miR-675 increase the invasive capacities of breast cancer cells in xenografted transgenic zebrafish models. In vitro, H19 and miR-675 enhance the cell migration and invasion, as well as colony formation. H19 seems 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 precursor H19, increases the stemness properties of breast cancer cells. Altogether, our data suggest that H19 and miR-675 could enhance the aggressiveness of breast cancer cells through both common and different mechanisms.

Regulation of Human Breast Cancer by the Long Non-Coding RNA H19.

Breast cancer is one of the most common causes of cancer related deaths in women. Despite the progress in early detection and use of new therapeutic targets associated with development of novel therapeutic options, breast cancer remains a major problem in public health. Indeed, even if the survival rate has improved for breast cancer patients, the number of recurrences within five years and the five-year relative survival rate in patients with metastasis remain dramatic. Thus, the discovery of new molecular actors involved in breast progression is essential to improve the management of this disease. Numerous data indicate that long non-coding RNA are implicated in breast cancer development. The oncofetal lncRNA H19 was the first RNA identified as a riboregulator. Studying of this lncRNA revealed its implication in both normal development and diseases. In this review, we summarize the different mechanisms of action of H19 in human breast cancer.