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

نویسندگان

چکیده

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

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2022

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2022.09.479