Cutaneous squamous cell carcinoma (cSCC) is one of the most common and fastest increasing forms of cancer worldwide with metastatic potential. Long non-coding RNAs (lncRNAs) are a group of RNA molecules with essential regulatory functions for both physiological and pathological processes. In this study, we identified plasmacytoma variant translocation 1 (PVT1) as a lncRNA upregulated in cSCC compared to healthy skin and to precancerous lesions (actinic keratosis). In situ hybridization analysis of PVT1-expression on a large cohort of cSCCs and precancerous lesions revealed that increased PVT1-expression is associated with the invasive phenotype. CRISPR-Cas9-deletion of the entire PVT1 locus resulted in impaired cell proliferation, colony formation and tumor spheroid formation abilities of cSCC cells. Interestingly, CRISPR-Cas9-mediated deletion of exon 7 of PVT1 resulted in a similar phenotype as the deletion of the entire PVT1 locus. Moreover, antisense oligonucleotide-mediated knockdown of the PVT1 transcript impaired cell proliferation, single cell colony formation, tumor spheroid formation, and invasion of cSCC cells and increased apoptosis suggesting that these effects are not due to deletion of genetic elements in the PVT1-locus. Finally, deletion of PVT1 impaired primary cSCC tumor growth in the xenograft model of cancer. Together, our study provides evidence for the oncogenic role of the PVT1 transcript in cSCC and offers a potential point of therapeutic intervention for cSCC.

ESDR431 - PVT1 is overexpressed in cutaneous squamous cell carcinoma and acts as an oncogenic long non-coding RNA

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.