Abstract 1098: MiR-203 suppresses cutaneous squamous cell carcinoma growth and targets the myc oncogene

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in man and accounts for approximately 20% of non-melanoma skin cancers. Although most cSCC are benign, poorly differentiated cSCC poses a significant risk of metastasis and death. To date, little is known about the difference in molecular background between low-risk and high risk cSCC. MicroRNAs are short regulatory RNAs that can regulate gene expression and cellular functions. Here we demonstrate for the first time that the expression of miR-203 in cSCC correlates with tumor differentiation grade, being down-regulated in poorly but not in moderately or well differentiated cSCC. In vitro, miR-203 causes a delay in G1 to S phase transition and suppresses cell proliferation in human cSCC cells. Furthermore, miR-203 suppresses scratch-wound closure, cell migration, cell invasion, colony forming ability and angiogenesis-inducing capacity of cSCC cells. Transcriptomic analysis of cSCC cells with ectopic overexpression of miR-203 reveals dramatic changes in gene networks related to carcinogenesis, with significant suppression of genes with known oncogenic functions (e.g. PCNA, EGFR, HGF). Using luciferase reporter assays and site-specific mutagenesis, we identify c-MYC as a novel target of miR-203. Highlighting the importance of c-MYC within miR-203-regulated gene network, in rescue experiments overexpression of c-MYC reverses miR-203-induced growth arrest in cSCC. In vivo, overexpression of miR-203 in cSCC cell lines result in reduced xenograft tumor volume and decreased vessel density. Together our data show that miR-203 acts a tumor suppressor in cSCC, affecting several oncogenic and angiogenic mechanisms. Importantly, its restoration may provide therapeutic benefit in particular in poorly differentiated cSCC. Citation Format: Warangkana Lohcharoenkal, Masako Harada, Jakob Loven, Florian Meisgen, Ning Xu Landen, Lingyun Zhang, Liisa Nissinen, Veli-Matti Kahari, Mona Stahle, Eniko Sonkoly, Dan Grander, Marie Arsenian-Henriksson, Andor Pivarcsi. MiR-203 suppresses cutaneous squamous cell carcinoma growth and targets the myc oncogene. [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 1098.