H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells

Abstract

The long non-coding RNA H19 is highly expressed in several cancers, and the functions of H19 vary among cancer cell types. Recently, we reported that H19 contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells and that inhibition of H19 reduces metastasis in vivo. However, the molecular mechanisms underlying the metastasis-promoting role of H19 in PDAC cells remain poorly elucidated. In this study, we clarified the mechanisms by which H19 regulates PDAC metastasis, with a focus on cancer stem cells (CSCs), by using H19-overexpressing and knockdown PDAC cells. Whereas the sphere-formation and invasion abilities of PDAC cells depended on H19 expression levels, other CSC characteristics of the cells, including stemness-marker expression and anticancer-drug resistance, were unaffected by H19 levels. Furthermore, metalloproteinase activity, a key mediator of invasion, was also independent of H19 expression. By contrast, H19 promoted cell adhesion through regulation of integrin and CD24 expression. Notably, the increased adhesion of H19-overexpressing cells was blocked by an anti-β1-integrin antibody, and this resulted in the inhibition of sphere formation and invasion. Thus, H19 plays critical roles in the CSC self-renewal and cell adhesion of PDAC that lead to invasion and metastasis. Our findings suggest that H19 represents a novel therapeutic target for the metastasis of pancreatic cancer.