miR-203 promotes HaCaT cell overproliferation through targeting LXR-α and PPAR-γ

作者：Yueyuan Xiao, Haizhen Wang, Chang Wang, Bijun Zeng, Xueyong Tang, Yujin Zhang, Youhua Peng, Meijunzi Luo, Pan Huang, Zhibo Yang · 发表于：Cell Cycle · 年份：2020 · DOI：10.1080/15384101.2020.1783934 · 被引用次数：30 · 研究领域：Cytokine Signaling Pathways and Interactions、NF-κB Signaling Pathways、Immunotherapy and Immune Responses

Psoriasis is an immune-mediated chronic inflammatory skin disease. Keratinocyte hyperproliferation has been regarded as a significant event in psoriasis pathogenesis. Considering the vital role of miRNA-mediated mRNA repression in psoriasis pathogenesis, in the present study, we attempted to investigate the mechanism of keratinocyte overproliferation from the point of miRNA-mRNA regulation. Both online microarray expression profiles and experimental results indicated that the expression of LXR-α and PPAR-γ was downregulated in psoriasis lesion skin. LXR-α or PPAR-γ overexpression alone was sufficient to inhibit keratinocyte proliferation, decrease KRT5 and KRT14 protein levels and increase KRT1 and KRT10 protein levels. miR-203 negatively regulated LXR-α and PPAR-γ expression through direct targeting. miR-203 inhibition exerted the opposite effects to LXR-α or PPAR-γ overexpression on HaCaT cells. More importantly, LXR-α or PPAR-γ overexpression could markedly remarkably attenuate the effects of miR-203 overexpression in keratinocytes, indicating that miR-203 promotes keratinocyte proliferation by targeting LXR-α and PPAR-γ. In conclusion, the miR-203-LXR-α/PPAR-γ axis modulates the proliferation of keratinocytes and might be a novel target for psoriasis treatment, which needs further in vivo investigation.