Downregulation of miR-885-5p Promotes NF-KB Pathway Activation and Immune Recruitment in Cutaneous Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) has a specific microRNA expression profile. MiR-885-5p has been found to be downregulated in the epidermis of CLE lesions; however, its biological role in the disease has not been studied. In this study, we show that miR-885-5p is markedly reduced in CLE keratinocytes (KCs) with IFN-a and UVB being strong miR-885-5p regulators in vitro. Microarray expression profiling of anti-miR-885-5p-transfected KCs identified PSMB5 as a direct target. Specific inhibition of miR-885-5p increased epidermal proliferation by modulating keratin 16 gene K16, BIRC5, TP63, and CDK4 proliferative genes and promoted NF-kB signaling pathway in human primary KCs by increasing IkBa degradation. Silencing PSMB5 rescued the effect of miR-885-5p inhibition, indicating that miR-885-5p regulates proliferation and NF-kB activation by targeting PSMB5 in KCs. In addition, inhibition of miR-885-5p increased the ability of KCs to attract leukocytes in a PSMB5-independent manner. We identified TRAF1 as another direct target, and its silencing reduced leukocyte migration. Collectively, our findings suggest that UVB and IFN-alpha downregulate miR-885-5p in CLE KCs, leading to epidermal inflammation by NF-kB activity enhancement and proliferation through PSMB5 and immune recruitment through TRAF1. Our data indicate that miR-885-5p is a potential therapeutic target in CLE.

Automated summary

This study found that miR-885-5p expression is significantly reduced in the epidermis of cutaneous lupus erythematosus (CLE) lesions. IFN-a and UVB are strong regulators of miR-885-5p. Inhibition of miR-885-5p promotes epidermal inflammation and proliferation through PSMB5 and immune recruitment through TRAF1, respectively.