NF-[kappa]B-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis

• Published in: Nature communications 2015-07, Vol.6, p.7652
• Main Authors: Yan, Sha, Xu, Zhenyao, Lou, Fangzhou, Zhang, Lingyun, Ke, Fang, Bai, Jing, Liu, Zhaoyuan, Liu, Jinlin, Wang, Hong, Zhu, Huiyuan, Sun, Yang, Cai, Wei, Gao, Yuanyuan, Su, Bing, Li, Qun, Yang, Xiao, Yu, Jianxiu, Lai, Yuping, Yu, Xue-zhong, Zheng, Yan, Shen, Nan, Chin, Y Eugene, Wang, Honglin
• Format: Article
• Language: English
• ISSN: 2041-1723
• DOI: 10.1038/ncomms8652

NF-κB is constitutively activated in psoriatic epidermis. However, how activated NF-κB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-κB activation triggered by inflammatory cytokines induces the transcription of microRNA (miRNA) miR-31, one of the most dynamic miRNAs identified in the skin of psoriatic patients and mouse models. The genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Furthermore, protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. The inhibition of ppp6c is functionally important for miR-31-mediated biological effects. Moreover, NF-κB activation inhibits ppp6c expression directly through the induction of miR-31, and enhances keratinocyte proliferation. Thus, our data identify NF-κB-induced miR-31 and its target, ppp6c, as critical factors for the hyperproliferation of epidermis in psoriasis.