Deciphering the Role of Non-Coding RNAs in Epidermal Carcinogenesis

Grantee: Andor Pivarcsi, Associate Professor, Karolinska Institutet, Stockholm, Sweden

Amount: DKK 4,164,300

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential, which accounts for 20% of all skin cancer-related deaths.

Patients with advanced tumors lack efficient treatment options, thus, there is an urgent medical need to find novel therapeutic approaches.

Long noncoding RNAs (lncRNAs) represent a crucial but as yet largely unexplored layer of gene regulation. We hypothesize that alterations in lncRNA-networks contribute to malignant progression and the that modulation of lncRNA expression can have therapeutic relevance.

Recently, we have performed a comprehensive RNAseq analysis in cSCC and identified a set of novel lncRNAs with altered expression in cSCC and whose functions are poorly characterized or completely unknown. These lncRNAs represent potential regulators of epidermal homeostasis and carcinogenesis.

In this study, we will explore the function of the identified lncRNAs in loss- and gain-of-function studies using in vitro and in vivo experimental models of cancer and differentiation, in vivo modulation of lncRNA-activity by delivery of antisense oligonucleotides (ASOs).

Additionally, we will identify the pathways regulated by cSCC-associated lncRNAs and define their mechanism of action by the biochemical characterization of binding partners.

Results of the proposed project will reveal the role of lncRNAs in epidermal carcinogenesis and pave the way towards the use of ASO-based be therapy of skin cancer.