SHARPIN, as a tumor-associated gene, is involved in the metastatic process of many kinds of tumors. Herein, we studied the function of Shank-associated RH domain interacting protein (SHARPIN) in melanoma metastasis and the relevant molecular mechanisms. We found that SHARPIN expression was increased in melanoma tissues and activated the process of proliferation, migration, and invasion in vitro and in vivo, resulting in a poor prognosis of the disease. Functional analysis demonstrated that SHARPIN promoted melanoma migration and invasion by regulating Ras-associated protein-1(Rap1) and its downstream pathways, including p38 and JNK/c-Jun. Rap1 activator (8-pCPT-2'-O-Me-cAMP) and inhibitor (ESI-09 and farnesylthiosalicylic acid-amide) treatments could partially rescue invasion and migration of tumor cells. Additionally, SHARPIN expression in cell lines and public datasets also indicated that molecules other than BRAF and N-RAS may contribute to SHARPIN activation. In conclusion, our broad-in-depth work suggests that SHARPIN promotes melanoma development via p38 and JNK/c-Jun pathways through upregulation of Rap1 expression.

Acne is the eighth most frequent disease worldwide. Inflammatory response runs through all stages of acne. It is complicated and is involved in innate and adaptive immunity. This study aimed to explore the candidate genes and their relative signaling pathways in inflammatory acne using data mining analysis. Microarray data GSE6475 and GSE53795, including 18 acne lesion tissues and 18 matched normal skin tissues, were obtained. Differentially expressed genes (DEGs) were filtered and subjected to functional and pathway enrichment analyses. Protein–protein interaction (PPI) network and module analyses were also performed based on the DEGs. In this work, 154 common DEGs, including 145 upregulated and 9 downregulated, were obtained from two microarray profiles. Gene Ontology and pathway enrichment of DEGs were clustered using significant enrichment analysis. A PPI network containing 110 nodes/DEGs was constructed, and 31 hub genes were obtained. Four modules in the PPI network, which mainly participated in chemokine signaling pathway, cytokine–cytokine receptor interaction, and Fc gamma R-mediated phagocytosis, were extracted. In conclusion, aberrant DEGs and pathways involved in acne pathogenesis were identified using bioinformatic analysis. The DEGs included FPR2, ITGB2, CXCL8, C3AR1, CXCL1, FCER1G, LILRB2, PTPRC, SAA1, CCR2, ICAM1, and FPR1, and the pathways included chemokine signaling pathway, cytokine–cytokine receptor interaction, and Fc gamma R-mediated phagocytosis. This study could serve as a basis for further understanding the pathogenesis and potential therapeutic targets of inflammatory acne.

Three methods are currently available to reconstitute hair follicles in mice. Direct comparisons have yet to be made to determine which method is most efficient. In this study, mouse epithelial cells (MECs) and mouse dermal cells (MDCs) were grafted onto the dorsal skin of nude mice using the chamber, flap or patch assays. Comparisons were made based on gross, scanning electron microscopic and histological observations. MDCs alone induced hair follicle reconstitution with the production of hairs yielding false‐positive results caused by contamination by hair follicle remnants. Neither primary MECs nor cultured MDCs alone formed hair follicles but did result in hair follicle formation when mixed together. Frozen MECs or MDCs resulted in decreased hair follicle–inductive activity but could still regenerate hairs. The hair patch assay was the quickest model (20 ± 3 days) to determine whether cell mixtures would reconstitute hair follicles that produce hairs; however, the hair follicles were randomly orientated and often associated with foreign body granulomas. The flap assay took the longest time (29 ± 2 days) to produce follicles and hairs to develop with a clinically natural appearance, but an epidermal sheet was needed. The chamber assay was the most labour‐intensive and cell number–dependent procedure but follicles developed in a dense, clinically normal manner.