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Background: Chronic actinic dermatitis (CAD) is an immune‐mediated photo‐allergic skin disease. In the clinic, the treatment of this disease is hampered by the lack of proper understanding of the skin barrier dysfunction mechanism. Objective: To illuminate the mechanism of skin barrier dysfunction in CAD. Methods: Transcriptome sequencing and protein profiling were used to detect skin barrier injury‐related genes. RNA pull down, a promoter‐reporter gene assay, and chromatin isolation by RNA purification‐sequencing were used to elucidate the effect of WAKMAR2 in skin barrier functionality. Results: Transcriptome sequencing from patient's tissues showed a significantly decreased expression of WAKMAR2. Down‐regulation of WAKMAR2 destroyed the keratinocyte barrier. Moreover, WAKMAR2 can directly bind to the c‐Fos protein. This novel long non‐coding RNA (LncRNA)‐protein complexes were targeted to the CLDN1 promotor. Overexpression of WAKMAR2 enhanced the promoter activity of CLDN1, while the addition of AP‐1 inhibitor could reverse this phenomenon. Furthermore, our in vivo results suggested that expression of WAKMAR2 was required for the repair of skin damage in mice induced by ultraviolet irradiation. Conclusions: We identified a crucial LncRNA (WAKMAR2) for the protection of the skin barrier in vitro and in vivo. Mechanically, it can specifically interact with c‐Fos protein for the regulation of CLDN1, a finding which could be applied for CAD treatment. [ABSTRACT FROM AUTHOR]

Cullin1 (Cul1) serves as a rigid scaffold in the SCF (Skp1/Cullin/Rbx1/F-box protein) E3 ubiquitin ligase complex and has been found to be overexpressed in melanoma and to enhance melanoma cell proliferation by promoting G1-S phase transition. However, the underlying mechanisms involved in the regulation of melanoma cell proliferation by Cul1 remain poorly understood. In the present study, we found that Cul1 promoted mTORC1 activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR. We further showed that suppression of the eIF4F complex assembly profoundly inhibited the promoting effect of Cul1 on melanoma cell proliferation, while enhancement of the eIF4F complex activity reversed the inhibitory effect of Cul1 depletion on melanoma cell proliferation, indicating that Cul1 contributes to melanoma cell proliferation by activating cap‑dependent translation. These data elucidate the role of Cul1 in cap-dependent translation and improves our understanding of the underlying mechanisms involved in the regulation of melanoma cell proliferation by Cul1.