Super Enhancer-Regulated LINC00094 ( SERLOC ) 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 BRD3OS , also named LINC00094 , in cutaneous squamous cell carcinoma (cSCC). Elevated BRD3OS ( LINC00094 ) 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 BRD3OS ( LINC00094 ) was noted in tumor cells in cSCCs and their metastases compared to normal skin, actinic keratoses, and cSCCs in situ. Higher BRD3OS ( LINC00094 ) expression was noted in metastatic cSCCs than in non-metastatic cSCCs. RNA-seq analysis after BRD3OS ( LINC00094 ) knockdown revealed significantly regulated GO terms Cell-matrix adhesion , Basement membrane , Metalloendopeptidase activity , and KEGG pathway Extracellular matrix-receptor interaction. Among the top-regulated genes were MMP1 , MMP10 , and MMP13 . Knockdown of BRD3OS ( LINC00094 ) 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, BRD3OS ( LINC00094 ) was named SERLOC (super enhancer and ERK1/2-Regulated Long Intergenic non-protein coding transcript Overexpressed in Carcinomas). These results reveal the role of SERLOC in cSCC invasion and identify it as a potential therapeutic target in advanced cSCC.