Up-regulated lncRNA-MSX2P1 promotes the growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7
Up-regulated lncRNA-MSX2P1 promotes the growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7
复制标题
上调的lncRNA-MSX2P1通过抑制miR-6731-5p和激活S100A7促进IL-22刺激的角质形成细胞的生长
DOI：
10.1016/j.yexcr.2018.01.014
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发表时间：
2018-02-15
影响因子：
3.7
通讯作者：
Sun, Qing
中科院分区：
文献类型：
--
作者：
Qiao, Meng;Li, Ronghua;Sun, Qing
Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for shared miRNAs and play critical roles in disease development. Psoriasis is a long-lasting, recurring chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. The keratinocyte response is triggered by the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT) cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining to determine the pathological changes in skin cells and immunohistochemistry to evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect the expression levels of MSX2P1 and S100A7. We down-regulated the expression of MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation, cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin V-FITC/PI staining, respectively. In addition, we used the luciferase reporter gene assay to determine the relationships between MSX2P1 or miR-6731-5p and S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up-regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22, compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p-S100A7 for further study. H&E staining exhibited characteristic features specific to psoriatic lesions. Immunohistochemistry demonstrated significantly increased expression levels of S100A7 in psoriatic lesions, compared with normal skin tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of S100A7, IL-12 beta, IL-23, HLA-C, CCHCR1, TNF-alpha, and NF-kappa B proteins. Our data demonstrated that MSX2P1 facilitate the progression and growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential novel therapeutic target for the future treatment of psoriasis.
