MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

Blog Article

Morphogenesis is crucial to initiate physiological development and tumor invasion.Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44.We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs.Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure.Protein analysis indicated that miR-328 repressed CD44 expression.

Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328.Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were Hoodie present on the surface of zonating structures while the control cells stayed in the middle.MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs.In vivo experiments showed that CD44-silencing #9 VERY LIGHT BLOND cells appeared as layers on the surfaces of nodules or zonating structures.Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins.

Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.