Background MicroRNAs (miRNAs) target genes involved in the hyperproliferation of keratinocytes or immune dysfunction of psoriasis. This study prospectively determined the involvement of miR-183-3p in the pathogenesis of psoriasis. Methods Differentially expressed miR-183-3p between psoriatic lesional and non-lesional skin were determined by quantitative RT-PCR and in situ hybridization (ISH). CCK8 and wound healing assays were performed to assess cell viability and migration of human keratinocyte cell line (HaCaT). The target of miR-183-3p was validated by luciferase activity assay. Results Lower miR-183-3p expression was observed in psoriatic lesional skin compared to psoriatic non-lesional skin. MiR-183-3p over-expression inhibited the viability and migration of HaCaT cells, while inhibition of miR-183-3p promoted the viability and migration of HaCaT cells. Moreover, miR-183-3p could bind to the 3′ UTR of GAB1 (growth factor receptor binding 2-associated binding protein 1) and decrease the mRNA and protein expression of GAB1 in HaCaT cells. In addition, higher GAB1 expression was observed in psoriatic lesional skin than psoriatic non-lesional skin. Conclusion MiR-183-3p exhibited inhibition property in the proliferation and migration of HaCaT cells via down-regulation of GAB1, suggesting the potential therapeutic strategy for psoriasis.

中文翻译：

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miR-183-3p通过抑制GAB1抑制银屑病角质形成细胞的增殖和迁移

背景 MicroRNA (miRNA) 靶向参与角质形成细胞过度增殖或银屑病免疫功能障碍的基因。本研究前瞻性地确定了 miR-183-3p 在银屑病发病机制中的参与。方法通过定量RT-PCR和原位杂交（ISH）检测银屑病皮损和非皮损皮肤之间差异表达的miR-183-3p。进行 CCK8 和伤口愈合测定以评估人角质形成细胞系 (HaCaT) 的细胞活力和迁移。miR-183-3p 的靶标通过荧光素酶活性测定进行验证。结果与银屑病非病变皮肤相比，在银屑病病变皮肤中观察到较低的 miR-183-3p 表达。MiR-183-3p 过表达抑制了 HaCaT 细胞的活力和迁移，而抑制 miR-183-3p 促进了 HaCaT 细胞的活力和迁移。此外，miR-183-3p 可以与 GAB1（生长因子受体结合 2 相关结合蛋白 1）的 3' UTR 结合并降低 HaCaT 细胞中 GAB1 的 mRNA 和蛋白表达。此外，在银屑病皮损皮肤中观察到的 GAB1 表达高于银屑病非皮损皮肤。结论 MiR-183-3p 通过下调 GAB1 对 HaCaT 细胞的增殖和迁移表现出抑制作用，提示银屑病的潜在治疗策略。在银屑病皮损皮肤中观察到比银屑病非皮损皮肤更高的 GAB1 表达。结论 MiR-183-3p 通过下调 GAB1 对 HaCaT 细胞的增殖和迁移表现出抑制作用，提示银屑病的潜在治疗策略。在银屑病皮损皮肤中观察到比银屑病非皮损皮肤更高的 GAB1 表达。结论 MiR-183-3p 通过下调 GAB1 对 HaCaT 细胞的增殖和迁移表现出抑制作用，提示银屑病的潜在治疗策略。