Abstract 982: Long non-coding RNA PICSAR promotes growth of cutaneous squamous cell carcinoma by regulating ERK1/2 activity

Abstract

Abstract Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Long non-coding RNAs (lncRNAs) are involved in various biological processes, and their role in cancer progression is emerging. The aim of this study was to find and characterize new biomarkers for evaluating the risk of progression and metastasis of cSCC and identify novel therapeutic targets for recurrent and metastatic cSCC. RNA-sequencing of cSCC cells (n = 8) and normal human epidermal keratinocytes (NHEKs, n = 4) revealed overexpression of a previously uncharacterized long intergenic non-coding RNA (lincRNA), LINC00162 in cSCC cells. Analysis of tissue sections by RNA in situ hybridization showed that LINC00162 is specifically expressed by tumor cells in cSCCs but not by keratinocytes in normal skin in vivo. The expression of LINC00162 in cSCC cells was upregulated by inhibition of the p38α and p38δ MAPKs using BIRB796 or p38α and p38δ specific siRNAs. Knockdown of LINC00162 inhibited proliferation and migration of cSCC cells, and suppressed the growth of human cSCC xenografts in vivo. Furthermore, knockdown of LINC00162 inhibited ERK1/2 activity and upregulated expression of dual specificity phosphatase DUSP6 in cSCC cells. Based on these observations, LINC00162 was named PICSAR (P38 Inhibited Cutaneous Squamous cell carcinoma Associated lincRNA). Our results provide mechanistic evidence for the role of PICSAR in promoting cSCC progression via activation of ERK1/2 signaling pathway by downregulating DUSP6 expression. These results also identify PICSAR as a novel biomarker and putative therapeutic target in cSCC. Citation Format: Minna Piipponen, Liisa Nissinen, Mehdi Farshchian, Pilvi Riihilä, Atte Kivisaari, Markku Kallajoki, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kähäri. Long non-coding RNA PICSAR promotes growth of cutaneous squamous cell carcinoma by regulating ERK1/2 activity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 982.