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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Cutaneous papillomaviruses infection rewires fatty-acid metabolism
Xiaoyan Liu1, Dan Li2, Fangzhou Cai2
1Department of Dermatology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Background:
Cutaneous warts are common HPV-induced lesions with limited treatments for recalcitrant cases. Fatty-acid metabolism (FAM) maintains epidermal homeostasis, but whether papillomavirus infection actively suppresses FAM programs and whether restoring FAM-related regulators can modulate keratinocyte dysfunction remain unclear.
Methods:
We established a murine MmuPV1 wart model and performed bulk RNA-seq. FAM-related DEGs were identified via network analysis and machine learning. Immune infiltration was assessed by CIBERSORT. In vitro validation used HPV16 E6/E7-transfected HaCaT cells.
Results:
Transcriptome analysis revealed significant suppression of FAM pathways in wart lesions. Four key FAM-related differentially expressed genes (Nr1h3, Dgat1, Scd1, and Fabp4) were identified from RNA-seq-based bioinformatic analyses and further supported by in vitro E6/E7-related expression assays. In vitro, HPV16 E6/E7 expression reduced these genes in HaCaT keratinocytes. NR1H3 overexpression partially attenuated E6/E7-induced proliferation and differentiation abnormalities, lipid-droplet accumulation, and IL-6/CCL2 secretion, with partial restoration of ABCA1 expression and inhibition of NF-kB activation.
Conclusions:
Papillomavirus infection is associated with coordinated suppression of FAM-related programs. NR1H3, Dgat1, Scd1, and Fabp4 represent candidate metabolic regulatory nodes; their therapeutic relevance requires further in vivo validation.
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