Long-term exposure to the sun UV-radiation is the leading cause for the
development of skin cancer. Keratinocyte-derived cutaneous squamous cell
carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is
increasing globally. Although the most frequent mutational targets in cSCC
development have been characterized, a comprehensive understanding of the
molecular events in cSCC pathogenesis remains incomplete.

There is an obvious need for clinically useful prognostic biomarkers and
therapeutic targets for recurrent and metastatic cSCCs. Long non-coding RNAs
(lncRNAs) are a largely uncharacterized group of regulatory RNAs involved in
various biological processes and their role in cancer progression is emerging.
However, their role in cSCC is largely unknown. The main objective of this thesis
was to investigate lncRNAs in order to identify new biomarkers for progression of
cSCC and characterize novel therapeutic targets for recurrent and metastatic cSCC.

In this study two tumorigenic lncRNAs in cSCC were identified, and based on
their expression and function and with the permission of the HUGO Gene
Nomenclature Committee they were named PICSAR and PRECSIT. They are
specifically upregulated in cSCC cells in culture and in vivo and they contribute to
cSCC progression by distinct mechanisms. PICSAR promotes cSCC cell growth by
activating ERK1/2 via suppression of DUSP6 expression. Furthermore, PICSAR
regulates adhesion and migration of cSCC cells by regulating integrin expression.
PRECSIT expression in cSCC cells was shown to be regulated by the p53 pathway.
Additionally, PRECSIT was found to regulate invasion of cSCC cells by regulating
STAT3 signaling and expression of MMP-1, MMP-13, MMP-13, and MMP-10.

In conclusion, lncRNAs PICSAR and PRECSIT may serve as novel biomarkers
and putative therapeutic targets in cSCC.