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.
Department of Dermatology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Ward 9-124, Chicago, IL 60611, USA.
Jia
J
Yu
Han
H
Peng
Qing
Q
Ruan
Anees
A
Fatima
Spiro
S
Getsios
Robert M
RM
Lavker
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics*; D006197:Hair / Q000166:cytology / Q000378:metabolism*; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D017931:DNA Primers; D035683:MicroRNAs