Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Nanchong City, 637000, Sichuan Province, China.
Hereditas. 2020 Jul 10;157(1):28. doi: 10.1186/s41065-020-00138-w.
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.
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.
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.
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.
MicroRNAs (miRNAs) 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。本研究前瞻性确定 miR-183-3p 在银屑病发病机制中的作用。
通过定量 RT-PCR 和原位杂交 (ISH) 确定银屑病病变和非病变皮肤之间差异表达的 miR-183-3p。CCK8 和划痕愈合实验评估人角质形成细胞系 (HaCaT) 的细胞活力和迁移。通过荧光素酶活性测定验证 miR-183-3p 的靶标。
与银屑病非病变皮肤相比,银屑病病变皮肤中 miR-183-3p 的表达较低。miR-183-3p 过表达抑制 HaCaT 细胞的活力和迁移,而抑制 miR-183-3p 则促进 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,与银屑病非病变皮肤相比,银屑病病变皮肤中 GAB1 的表达更高。
miR-183-3p 通过下调 GAB1 表现出对 HaCaT 细胞增殖和迁移的抑制作用,提示其可能成为银屑病的治疗策略。