title: Long Noncoding RNA PICSAR Promotes Growth of Cutaneous Squamous Cell Carcinoma by Regulating ERK1/2 Activity.
abstract: Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Long noncoding RNAs (lncRNA) are involved in various biological processes, and their role in cancer progression is emerging. Whole transcriptome analysis of cSCC cells (n = 8) and normal human epidermal keratinocytes (n = 4) revealed overexpression of long intergenic ncRNA (LINC00162) in cSCC cells. The expression of LINC00162 in cSCC cells was upregulated by inhibition of the p38α and p38δ mitogen-activated protein kinases. Analysis of tissue sections by RNA in situ hybridization showed that LINC00162 is specifically expressed by tumor cells in cSCCs but not by keratinocytes in normal skin in vivo. Knockdown of LINC00162 inhibited proliferation and migration of cSCC cells, and suppressed the growth of human cSCC xenografts in vivo. Furthermore, knockdown of LINC00162 inhibited extracellular signal-regulated kinase 1/2 activity and upregulated expression of dual specificity phosphatase 6 (DUSP6) in cSCC cells. Based on these observations, LINC00162 was named p38 inhibited cutaneous squamous cell carcinoma associated lincRNA (PICSAR). Our results provide mechanistic evidence for the role of PICSAR in promoting cSCC progression via activation of extracellular signal-regulated kinase 1/2 signaling pathway by downregulating DUSP6 expression. These results also identify PICSAR as a biomarker and putative therapeutic target in cSCC.
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Piipponen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Nissinen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Farshchian
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Riihilä
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Atte
authors.initials: A
authors.lastname: Kivisaari
authors.affiliation: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Kallajoki
authors.affiliation: Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Peltonen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Sirkku
authors.initials: S
authors.lastname: Peltonen
authors.affiliation: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland. Electronic address: veli-matti.kahari@utu.fi.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kähäri
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D054642:Dual Specificity Phosphatase 6 / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding; D012878:Skin Neoplasms / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C000610631:NLC1C lncRNA, human; D062085:RNA, Long Noncoding; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6