Department of Dermatology, The First Hospital of China Medical University, Shenyang, China.
Department of Dermatology, The Seventh People's Hospital of Shenyang, Shenyang, China.
Dermatology. 2021;237(4):568-578. doi: 10.1159/000510681. Epub 2021 Mar 18.
Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes.
Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed.
miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866-0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells.
miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.
银屑病的发病机制与炎症和免疫系统失调有关。微小 RNA（miR）-125a 与炎症和免疫密切相关；因此，我们推测它可能在银屑病的发病机制中发挥作用。本研究旨在探讨 miR-125a 与银屑病患者疾病严重程度和炎症的相关性，以及 miR-125a 对角质形成细胞增殖、凋亡及其靶信号通路的影响。
连续招募 60 例银屑病患者，采集皮损和非皮损皮肤组织标本。检测皮损和非皮损皮肤组织中的 miR-125a 及皮损皮肤组织中肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6 和 IL-17 mRNA 表达。然后，将 miR-125a 过表达、对照过表达、miR-125a 敲低和对照敲低质粒转染入 HaCaT 细胞。随后，评估细胞增殖、凋亡、IL-23R、JAK2 和 STAT3 表达。
与非皮损皮肤组织相比，皮损皮肤组织中 miR-125a 降低（p＜0.001），且 miR-125a 区分皮损皮肤组织与非皮损皮肤组织的曲线下面积为 0.917（95%CI 0.866-0.968）。miR-125a 在皮损皮肤组织中的表达与皮损体表面积（p=0.037）和银屑病面积和严重程度指数评分（p＜0.001）呈负相关。此外，miR-125a 与皮损皮肤组织中 TNF-α（p=0.001）、IL-1β（p=0.014）和 IL-17（p=0.003）呈负相关。在细胞实验中，miR-125a 过表达抑制增殖并促进凋亡，而 miR-125a 敲低则增强增殖并抑制凋亡。此外，miR-125a 负调控 HaCaT 细胞中的 IL-23R/JAK2/STAT3 通路。
miR-125a 可辅助疾病监测，可能具有成为银屑病治疗靶点的潜力。
