biostudies-literatureYu JNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNEI NIH HHSDermatology FoundationNational Institutes of HealthNIAMS NIH HHS3950-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC2996908biostudies-literatureUnknown24(10)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.FASEB journal : official publication of the Federation of American Societies for Experimental BiologyMicroRNA-205 promotes keratinocyte migration via the lipid phosphatase SHIP2.PMC2996908P30AR057216EY017536P30 AR057216R21 EY017536EY019463R01 EY019463Peng HLavker RMRuan QYu JFatima AGetsios SfalseMicroRNA-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.2010-01-01T00:00:00Z2010 Oct2025-04-05T15:53:11.508Z2019-03-27T00:01:28ZS-EPMC29969082053024810.1096/fj.10-157404