Super enhancers have been shown to present a role in tumorigenesis, indicating that they could be promising therapeutic targets for cancer treatment. Long noncoding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Here, the role of lncRNA LINC00094 in cutaneous squamous carcinoma (cSCC) was examined. Elevated LINC00094 expression was detected in cSCC cell lines, compared with normal human epidermal keratinocytes. The expression of LINC00094 in cSCC cells was downregulated by super enhancer inhibitors THZ1 and JQ1. Increased expression of LINC00094 was noted in tumor cells in invasive cSCC in vivo compared with cSCC in situ, actinic keratosis and normal skin. The basal expression of LINC00094 was upregulated by IL1-β and downregulated via MEK1/ERK1/2 pathway. RNA-seq analysis after LINC00094 knockdown revealed significantly regulated GO terms Cell-matrix adhesion, Extracellular matrix component, Basement membrane, Metalloendopeptidase activity, and KEGG pathway Extracellular matrix-receptor interaction. Among the top regulated genes were invasion-associated matrix metalloproteinases MMP1, MMP10 and MMP13. Knockdown of LINC00094 resulted in decreased production of MMP-1 and MMP-13 by cSCC cells in culture and suppressed invasion of cSCC cell through collagen I. Additionally LINC00094 silencing decreased the growth of human cSCC xenografts in vivo. These results provide evidence for the role of super enhancer-regulated LINC00094 in the progression of cSCC and identify it as a potential therapeutic target in this keratinocyte carcinoma.

Super enhancers have been shown to present a role in tumorigenesis, indicating that they could be promising therapeutic targets for cancer treatment. Long noncoding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Here, the role of lncRNA LINC00094 in cutaneous squamous carcinoma (cSCC) was examined. Elevated LINC00094 expression was detected in cSCC cell lines, compared with normal human epidermal keratinocytes. The expression of LINC00094 in cSCC cells was downregulated by super enhancer inhibitors THZ1 and JQ1. Increased expression of LINC00094 was noted in tumor cells in invasive cSCC in vivo compared with cSCC in situ, actinic keratosis and normal skin. The basal expression of LINC00094 was downregulated via MEK1/ERK1/2 pathway. RNA-seq analysis after LINC00094 knockdown revealed significantly regulated GO terms Cell-matrix adhesion, Extracellular matrix component, Basement membrane, Metalloendopeptidase activity, and KEGG pathway Extracellular matrix-receptor interaction. Among the top regulated genes were invasion-associated matrix metalloproteinases MMP1, MMP10 and MMP13. Knockdown of LINC00094 resulted in decreased production of MMP-1 and MMP-13 by cSCC cells in culture and suppressed invasion of cSCC cell through collagen I. Additionally LINC00094 silencing decreased the growth of human cSCC xenografts in vivo. These results provide evidence for the role of super enhancer-regulated LINC00094 in the progression of cSCC and identify it as a potential therapeutic target in this keratinocyte carcinoma.

ESDR465 - Super enhancer regulated LINC00094 upregulates the expression of metalloproteinases MMP-1 and MMP-13 and promotes invasion of cutaneous squamous cell carcinoma

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.