Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Dermatology, The Second People's Hospital of Guiyang, Guizhou, China.
Photodermatol Photoimmunol Photomed. 2021 Jul;37(4):269-277. doi: 10.1111/phpp.12647. Epub 2021 Jan 18.
Chronic actinic dermatitis (CAD) is a photoallergic skin disease with abnormal hyperplasia. At present, the mechanism of abnormal proliferation is not clear.
To explore possible mechanism of CAD proliferative lesions.
Immunohistochemistry (IHC) assay and small RNA sequencing were carried out. Quantitative real-time PCR (qRT-PCR) analysis was performed to evaluate expression levels of hsa-miR-221-3p and FOS. The interaction between hsa-miR-221-3p and FOS was identified by dual-luciferase reporter assay. Expression of hsa-miR-221-3p also was detected by qRT-PCR after UVB irradiation. Influences of hsa-miR-221-3p and FOS on cell viability and apoptosis were assessed through a series of functional experiments and rescue experiments. Western blot analysis was used to detect protein expression of fos, Bax, Bcl-xL, and caspase-3.
Patients with CAD had marked epidermal hyperplasia. The expression of hsa-miR-221-3p was up-regulated in CAD while FOS was significantly down-regulated. Dual-luciferase reporter assay confirmed that hsa-miR-221-3p targeted FOS 3'UTR. Hsa-miR-221-3p induced by UVB ranged from 0 to 30 mJ. Moreover, hsa-miR-221-3p overexpression or FOS knockdown promoted cell proliferation and reduced cell apoptosis. Western blot showed that hsa-miR-221-3p negatively regulated fos, which regulated Bcl-xL/Bax. Cell proliferation caused by hsa-miR-221-3p overexpression or FOS knockdown could be reversed by Bcl-xL inhibitor.
Hsa-miR-221-3p induced by UVB targeted FOS 3'UTR, which played an important role in regulating proliferation and apoptosis of keratinocytes via Bcl-xL/Bax pathway; this may provide a new insight for CAD proliferative lesions.
慢性光化性皮炎（CAD）是一种光变应性皮肤病，具有异常增生。目前，异常增殖的机制尚不清楚。
探讨 CAD 增殖性病变的可能机制。
进行免疫组织化学（IHC）检测和小 RNA 测序。采用定量实时 PCR（qRT-PCR）分析评估 hsa-miR-221-3p 和 FOS 的表达水平。通过双荧光素酶报告基因检测鉴定 hsa-miR-221-3p 与 FOS 的相互作用。通过 qRT-PCR 检测 UVB 照射后 hsa-miR-221-3p 的表达。通过一系列功能实验和挽救实验检测 hsa-miR-221-3p 和 FOS 对细胞活力和细胞凋亡的影响。采用 Western blot 分析检测 fos、Bax、Bcl-xL 和 caspase-3 的蛋白表达。
CAD 患者表皮明显增生。CAD 中 hsa-miR-221-3p 的表达上调，而 FOS 的表达显著下调。双荧光素酶报告基因检测证实 hsa-miR-221-3p 靶向 FOS 3'UTR。UVB 诱导的 hsa-miR-221-3p 表达范围为 0 至 30 mJ。此外，hsa-miR-221-3p 过表达或 FOS 敲低促进细胞增殖，减少细胞凋亡。Western blot 显示 hsa-miR-221-3p 负调控 fos，fos 调节 Bcl-xL/Bax。hsa-miR-221-3p 过表达或 FOS 敲低引起的细胞增殖可被 Bcl-xL 抑制剂逆转。
UVB 诱导的 hsa-miR-221-3p 靶向 FOS 3'UTR，通过 Bcl-xL/Bax 途径在调节角质形成细胞增殖和凋亡中发挥重要作用；这可能为 CAD 增殖性病变提供新的见解。
