Super Enhancer-Regulated () Upregulates the Expression of MMP-1 and MMP-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma.

Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Super enhancers (SE) play a role in tumorigenesis and regulate the expression of specific lncRNAs. We examined the role of , also named , in cutaneous squamous cell carcinoma (cSCC). Elevated () expression was detected in cSCC cells, and expression was downregulated by SE inhibitors THZ1 and JQ1 and via the MEK1/ERK1/2 pathway. Increased expression of () was noted in tumor cells in cSCCs and their metastases compared to normal skin, actinic keratoses, and cSCCs in situ. Higher () expression was noted in metastatic cSCCs than in non-metastatic cSCCs. RNA-seq analysis after () knockdown revealed significantly regulated GO terms , , , and KEGG pathway Among the top-regulated genes were , , and . Knockdown of () resulted in decreased production of MMP-1 and MMP-13 by cSCC cells, suppressed invasion of cSCC cells through collagen I, and growth of human cSCC xenografts in vivo. Based on these observations, () was named (super enhancer and ERK1/2-Regulated Long Intergenic non-protein coding transcript Overexpressed in Carcinomas). These results reveal the role of in cSCC invasion and identify it as a potential therapeutic target in advanced cSCC.