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 thefunctions of H19 vary among cancer cell types. Recently, we reported that H19contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells andthat inhibition of H19 reduces metastasis in vivo. However, the molecular mechanismsunderlying the metastasis-promoting role of H19 in PDAC cells remain poorlyelucidated. In this study, we clarified the mechanisms by which H19 regulates PDACmetastasis, with a focus on cancer stem cells (CSCs), by using H19-overexpressingand knockdown PDAC cells. Whereas the sphere-formation and invasion abilitiesof PDAC cells depended on H19 expression levels, other CSC characteristics of thecells, including stemness-marker expression and anticancer-drug resistance, wereunaffected by H19 levels. Furthermore, metalloproteinase activity, a key mediator ofinvasion, was also independent of H19 expression. By contrast, H19 promoted celladhesion through regulation of integrin and CD24 expression. Notably, the increasedadhesion 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 playscritical roles in the CSC self-renewal and cell adhesion of PDAC that lead to invasionand metastasis. Our findings suggest that H19 represents a novel therapeutic targetfor the metastasis of pancreatic cancer.