Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family, and FABP5 were significantly upregulated in cSCC cells. Further experiments confirmed their upregulation and showed that S100A9 or FABP5 knockdown in cSCC cells inhibited their proliferation and migration through NF-κB pathway. Taken together, our data provide a valuable resource for deciphering the molecular pattern in UV-induced cSCC at a single-cell level and suggest that S100A9 and FABP5 may provide novel targets for therapeutic intervention of cSCC in the future.
Atopic dermatitis (AD) is a common chronic relapsing inflammatory disease. There is substantial evidence suggesting that noncoding RNAs have indispensable roles in the pathogenesis of AD. Exosomal transfer RNA-derived fragments (tRFs) have been identified as potential biomarkers for various disorders. However, the role of tRFs in AD has remained to be elucidated, which was thus the aim of the present study. Plasma samples from 23 pediatric patients with AD and 23 healthy controls were collected. Exosomes were successfully isolated from plasma according to the manufacturer's protocol. Small RNA sequencing was performed in 3 patients with AD and 3 controls, and 135 significantly differentially expressed plasma exosomal tRFs were identified, including 36 upregulated and 99 downregulated tRFs. Using the miRanda and RNAhybrid databases, 58,227 target genes of these 135 differentially expressed tRFs were predicted. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that these target genes of tRFs are involved in multiple functions and pathways associated with AD. Downregulation of tRF-28-QSZ34KRQ590K and tRF-33-Q99P9P9NH57SD3 were validated in 20 patients with AD and 20 controls by reverse transcription-quantitative PCR and tRF-28-QSZ34KRQ590K exhibited significance in the receiver operating characteristic curve analysis. The present study was the first to provide a tRF profile in AD and implied that plasma exosomal tRF-28-QSZ34KRQ590K may be a potential biomarker for pediatric patients with AD. The present study enhanced the understanding of the pathogenesis of AD and provided a novel marker for the diagnosis and targeted treatment of AD.
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