Cutaneous SCC (cSCC) represents the most frequently occurring cancer with metastatic potential accounting for 20% of all skin cancer-related deaths. The incidence of cSCC has been increasing alarmingly especially in Nordic countries. Long noncoding RNAs (lncRNAs) are transcripts that are longer than 200 nt, lack the potential to encode functional proteins and play important roles in gene regulation. In this study, we aimed to investigate the role of lncRNAs in the pathogenesis of cSCC. To identify potential clinically relevant lncRNAs in cSCC, we performed RNA sequencing in human cSCCs. One of the most upregulated lncRNA in cSCC was Plasmacytoma Variant Translocation 1 gene (PVT1). qRT-PCR in an independent set of human samples by confirmed the increased level of PVT in cSCC but no increase was observed in precancerous skin lesions (actinic keratosis), suggesting that increased PVT1 expression is associated with malignant transformation. Using single-molecule in situ hybridization (RNAScope), we demonstrated that PVT1 lncRNA is localized to the cell nucleus in cSCC cells. GapmeR-mediated knockdown of PVT1 lncRNA resulted in decreased cell proliferation and long-term capacity of growth as determined by EdU- and colony formation assays, respectively. Moreover, knockdown of PVT1 impaired the migration and invasion ability of SCC cells and increased apoptosis in cSCC cell lines in vitro. Although PVT1 has previously been reported to involved in the MYC-mediated cancer-promoting pathway through stabilizing MYC protein in other cancer types, our experiments showed that c-MYC protein stability was not significantly affected by PVT1 in cSCC cells, suggesting other modes of action in cSCC. Our results indicate that lncRNAs may play an important role in the pathogenesis of cSCC and PVT1 may play an oncogenic role in the disease.

ESDR255 - PVT1 is overexpressed and acts as an oncogenic long non-coding RNA in cutaneous squamous cell carcinoma

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING