Long non-coding RNAs (lncRNAs) have emerged as putative biomarkers and therapeutic targets in cancer. Here, we have examined the role of LINC00346 in keratinocyte-derived cutaneous squamous cell carcinoma (cSCC). LINC00346 expression was upregulated in cSCC cells compared to normal human epidermal keratinocytes. Elevated expression of LINC00346 was also noted in tumor cells in cSCC tissue sections in vivo as compared to cSCC in situ and actinic keratosis by RNA in situ hybridization, whereas LINC00346 expression in benign epidermal papilloma (seborrheic keratosis) and normal skin was very low. Immunohistochemical analysis of cSCC tissue sections and functional assays of cSCC cells in culture showed that LINC00346 expression is downregulated by p53. Knockdown of LINC00346 inhibited invasion of cSCC cells in culture and suppressed growth of human cSCC xenografts in vivo. LINC00346 knockdown inhibited expression of activated STAT3 and resulted in decreased expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-10, and MMP-13 in cSCC cells. Based on these observations LINC00346 was named p53 regulated carcinoma-associated STAT3-activating long intergenic non-protein coding transcript (PRECSIT). These results identify PRECSIT as a novel p53-regulated lncRNA, which promotes progression of cSCC via STAT3 signaling.

p53-regulated long non-coding RNA PRECSIT promotes progression of cutaneous squamous cell carcinoma via STAT3 signaling