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miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression
Biochemical Genetics ( IF 2.1 ) Pub Date : 2020-11-19 , DOI: 10.1007/s10528-020-09997-4
Tao Liu 1 , Xiaomei Feng 2 , Yongmei Liao 1
Affiliation  

Psoriasis is considered as a common chronic and relapsing inflammatory skin disease. MicroRNAs (miRNAs) were found to be related with psoriasis pathogenesis. Nevertheless, the function of miR-617 in psoriasis is still unclear. The miR-617 RNA level was detected using quantitative reverse transcription-PCR (qRT-PCR). Western blot analysis examined the protein level. Cell proliferation was analyzed via cell counting kit-8 (CCK-8) assay. Flow cytometry analysis detected cell cycle and apoptosis. The relationship between miR-617 and forkhead box protein O4 (FOXO4) was confirmed through dual luciferase assay. The miR-617 was up-regulated in psoriatic skin tissues and interleukin-22 (IL-22)-stimulated immortalized human keratinocyte HaCaT cells. Moreover, miR-617 mimics promoted proliferation, cell cycle, and suppressed apoptosis in IL-22-stimulated HaCaT cells. However, miR-617 inhibitor showed opposite effects. Additionally, FOXO4 was a target of miR-617. FOXO4 was down-regulated in psoriatic skin tissues and IL-22-stimulated HaCaT cells. Negative correlation between miR-617 and FOXO4 was identified. FOXO4 overexpression alleviated the effects of miR-617 proliferation, cell cycle and apoptosis in the IL-22-stimulated HaCaT cells. These results demonstrate that miR-617 increases the growth of IL-22-stimulated keratinocytes through targeting FOXO4, which provides a new therapeutic target for psoriasis.



中文翻译:


miR-617 通过调节 FOXO4 表达促进 IL-22 刺激的角质形成细胞的生长



牛皮癣被认为是一种常见的慢性和复发性炎症性皮肤病。 MicroRNA (miRNA)被发现与银屑病发病机制有关。然而,miR-617在银屑病中的功能仍不清楚。使用定量逆转录-PCR (qRT-PCR) 检测 miR-617 RNA 水平。蛋白质印迹分析检查了蛋白质水平。通过细胞计数试剂盒-8 (CCK-8) 测定法分析细胞增殖。流式细胞术分析检测细胞周期和细胞凋亡。通过双荧光素酶测定证实了 miR-617 和叉头盒蛋白 O4 (FOXO4) 之间的关系。 miR-617 在银屑病皮肤组织和白细胞介素 22 (IL-22) 刺激的永生化人角质形成细胞 HaCaT 细胞中上调。此外,miR-617 模拟物促进 IL-22 刺激的 HaCaT 细胞的增殖、细胞周期并抑制细胞凋亡。然而,miR-617抑制剂表现出相反的效果。此外,FOXO4 是 miR-617 的靶标。 FOXO4 在银屑病皮肤组织和 IL-22 刺激的 HaCaT 细胞中下调。 miR-617 和 FOXO4 之间呈负相关。 FOXO4 过表达减轻了 IL-22 刺激的 HaCaT 细胞中 miR-617 增殖、细胞周期和凋亡的影响。这些结果表明,miR-617通过靶向FOXO4来增加IL-22刺激的角质形成细胞的生长,这为银屑病提供了新的治疗靶点。

更新日期:2020-11-19
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