Abstract
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.
Original language | English (US) |
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Pages (from-to) | 3950-3959 |
Number of pages | 10 |
Journal | FASEB Journal |
Volume | 24 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2010 |
Keywords
- Cell signaling
- Cell survival
- Corneal epithelium
- Epidermis
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics