MicroRNA‐205 promotes keratinocyte migration via the lipid phosphatase SHIP2

microRNA‐205 (miR‐205) and miR‐184 coordinately regulate the lipid phosphatase SHIP2 for Akt survival signaling in keratinocytes. As the PI3K‐Akt pathway has also been implicated in regulating the actin cytoskeleton and cell motility, we investigated the role that these 2 miRNAs play in keratinocyte migration. We used antagomirs (antago) to reduce the levels of miR‐205 and miR‐184 in primary human epidermal keratinocytes (HEKs) and corneal epithelial keratinocytes (HCEKs) as well as direct SHIP2 silencing using siRNA oligos. Treatment of HEKs and HCEKs with antago‐205 increased SHIP2 levels and impaired the ability of these cells to seal linear scratch wounds compared with untreated or irrelevant‐antago treatments. In contrast, AKT signaling was enhanced and wounds sealed faster in HCEKs where miR‐184 was suppressed, enabling miR‐205 to inhibit SHIP2. Similar increases in migration were observed following direct SHIP2 silencing in HEKs. Furthermore, down‐regulation of miR‐205 resulted in an increase in Rho‐ROCKI activity, phosphorylation of the actin severing protein cofilin, and a corresponding diminution of filamentous actin. The connection among miR‐205, RhoA‐ROCKI‐cofilin inactivation, and the actin cytoskeleton represents a novel post‐translational mechanism for the regulation of normal human keratinocyte migration.—Yu, J., Peng, H., Ruan, Q., Fatima, A., Getsios, S., Lavker, R. M. MicroRNA‐205 promotes keratinocyte migration via the lipid phosphatase SHIP2. FASEB J. 24, 3950–3959 (2010). www.fasebj.org