Abstract
ABSTRACTLong non-coding RNAs (lncRNAs) regulate various cellular processes, and they have emerged as potential biomarkers and therapeutic targets in cancer. We have previously characterized the oncogenic role of lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA) in cutaneous squamous cell carcinoma (cSCC), the most common metastatic skin cancer. In this study, we show that knockdown of PICSAR in cSCC cells upregulates expression of α2, α5 and β1 integrins, resulting in increased cell adhesion and decreased cell migration on collagen I and fibronectin. In contrast, overexpression of PICSAR in cSCC cells downregulates expression of α2, α5 and β1 integrins on cell surface, resulting in decreased cell adhesion on collagen I and fibronectin and increased cell migration. These results demonstrate a novel mechanism for regulation of the expression of collagen and fibronectin binding integrins by lncRNA PICSAR, leading to altered adhesion and migration of cSCC cells.This article has an associated First Person interview with the first author of the paper.
Highlights
Long non-coding RNAs are a diverse and widely uncharacterized group of non-coding transcripts involved in cell regulation (Geisler and Coller, 2013)
We have recently identified and characterized Long non-coding RNAs (lncRNAs) PICSAR ( p38 inhibited cutaneous squamous cell carcinoma associated lincRNA), which is expressed by tumor cells in cSCC but not by keratinocytes in normal skin in vivo (Piipponen et al, 2016)
The cell tracking assay showed that silencing of PICSAR decreased migration of cSCC cells on collagen I and fibronectin compared to control siRNA transfected cells (Fig. 1A; Fig. S1A)
Summary
Long non-coding RNAs (lncRNAs) are a diverse and widely uncharacterized group of non-coding transcripts involved in cell regulation (Geisler and Coller, 2013). We show that knockdown of PICSAR in cSCC cells upregulates expression of α2, α5 and β1 integrins in cSCC cells, resulting in increased cell adhesion and decreased cell migration both on collagen I and fibronectin. Overexpression of PICSAR in cSCC cells downregulates expression of α2, α5 and β1 integrins on cell surface, resulting in decreased cell adhesion on collagen I and fibronectin and increased cell migration.
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