Piipponen Minna, Heino Jyrki, Kähäri Veli-Matti, Nissinen Liisa
Department of Dermatology, University of Turku and Turku University Hospital, FI-20520 Turku, Finland.
Western Cancer Center (FICAN West), University of Turku and Turku University Hospital, FI-20520 Turku, Finland.
Biol Open. 2018 Nov 14;7(11):bio037044. doi: 10.1242/bio.037044.
Long 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.
长链非编码RNA(lncRNAs)可调节多种细胞过程,并且已成为癌症中潜在的生物标志物和治疗靶点。我们之前已阐述了lncRNA PICSAR(p38抑制的皮肤鳞状细胞癌相关长链间质性RNA)在皮肤鳞状细胞癌(cSCC,最常见的转移性皮肤癌)中的致癌作用。在本研究中,我们发现敲低cSCC细胞中的PICSAR可上调α2、α5和β1整合素的表达,导致细胞在I型胶原和纤连蛋白上的黏附增加而迁移减少。相反,在cSCC细胞中过表达PICSAR可下调细胞表面α2、α5和β1整合素的表达,导致细胞在I型胶原和纤连蛋白上的黏附减少而迁移增加。这些结果证明了lncRNA PICSAR调节胶原和纤连蛋白结合整合素表达的新机制,导致cSCC细胞的黏附和迁移发生改变。本文配有对该论文第一作者的相关第一人称访谈。