MicroRNA-185 inhibits the proliferation and migration of HaCaT keratinocytes by targeting peroxisome proliferator-activated receptor β

MicroRNA-185通过靶向过氧化物酶体增殖激活受体β抑制HaCaT角质形成细胞的增殖和迁移

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作者:Jingzhe Yang, Pingyang Deng, Yonggang Qi, Xinshu Feng, Hailing Wen, Fengping Chen

Abstract

Proliferation and migration of keratinocytes are major processes of skin wound repair after injury. It has been indicated that microRNAs (miRNAs/miRs) are associated with the proliferation and migration of keratinocytes. However, the mechanism by which miR-185 affects these processes in keratinocytes remains unclear. In the present study, the expression level of miR-185 and peroxisome proliferator-activated receptor β (PPARβ) was examined by reverse transcription-quantitative PCR in HaCaT keratinocytes. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. Western blot analysis was used to detect the levels of cell proliferation, migration and PI3K/AKT signaling pathway-associated proteins. In addition, the migratory capacity of the cells was determined using Transwell assay. The target gene of miR-185 was verified using dual-luciferase reporter assay. The results indicated that overexpression of miR-185 inhibited proliferation, migration and activation of the PI3K/AKT signaling pathway in HaCaT keratinocytes. PPARβ was indicated to be a target of miR-185 and its overexpression promoted the proliferation and migration of HaCaT keratinocytes, while its knockdown exhibited the adverse effects. Furthermore, PI3K inhibitor LY294002 inhibited activation of the PI3K/AKT signaling pathway and decreased the proliferation and migration of HaCaT keratinocytes. In addition, overexpressed PPARβ reversed the suppressive effects of miR-185 overexpression on proliferation, migration and activation of the PI3K/AKT signaling pathway. In conclusion, the results of the present study demonstrated that miR-185 suppressed activation of the PI3K/AKT signaling pathway via targeting PPARβ, thereby regulating proliferation and migration in HaCaT keratinocytes. The present study provided a novel theoretical basis for the use of miR-185 as a target in wound repair.

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