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Medicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA1064585Homo sapiensxref:PubMed:38327798HERC6 is an Interferon stimulated gene and expressed by epidermal keratinocytes, yet its specific role in the skin remains unclear. In this investigation, we employed bulk RNA-sequencing to explore the broader impact of HERC6 in response to sensing of cytosolic DNA mimic, cGAMP or RNA agonist, TLR3. We observed an elevated number of differentially expressed genes in keratinocytes following HERC6 knockdown, and among them, several were associated with the Interferon signaling pathway, such as OAS1, IFIT3, and STAT2, showing increased expression in HERC6 knockdown keratinocytes when stimulated with cGAMP. Additionally, our findings revealed a dysregulation in the HIPPO pathway-related genes, particularly LATS1/2, in HERC6 knockdown keratinocytes. Utilizing bulk RNA-sequencing, we identified enriched Gene Ontology terms associated with the Interferon pathway and cytosolic sensing of foreign DNA in HERC6 knockdown keratinocytes, suggesting HERC6 as a negative regulator of Interferon signaling upon DNA sensing but not RNA. This data was instrumental in elucidating the regulatory functions of HERC6 in keratinocytes during the sensing of exogenous DNA or RNA mimics. Overall design: Three male (subjects 1, 2, and 3) and three female (subjects 4, 5, and 6) primary human keratinocytes were used to perform non-targeting control (NTC) or HERC6 knockdown using siRNA and stimulated with or without cGAMP or Poly(I:C).ENAfalseExpression data from primary human keratinocytes upon control or HERC6 knockdown using siRNA and stimulated in vitro with or without cGAMP or Poly(I:C)Expression data from primary human keratinocytes upon control or HERC6 knockdown using siRNA and stimulated in vitro with or without cGAMP or Poly(I:C)2025-09-242024-02-16PRJNA1064585GSE253221960638327798