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Long noncoding RNAs (lncRNAs) are a group of RNA molecules with essential regulatory functions in both physiological and pathological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the function and mode of action of lncRNA plasmacytoma variant translocation 1 (PVT1) in cSCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Quantitative reverse transcriptase polymerase chain reaction and single-molecule in situ hybridization were used to quantify the expression level of PVT1 in normal skin, premalignant skin lesions, actinic keratosis (AK) and primary and metastatic cSCCs. The function of PVT1 in cSCC was investigated both in vivo (tumour xenografts) and in vitro (competitive cell growth assay, 5-ethynyl-2\u2032-deoxyuridine incorporation assay, colony formation assay and tumour spheroid formation assay) upon CRISPR-Cas9-mediated knockout of the entire PVT1 locus, the knockout of exon 2 of PVT1, and locked nucleic acid (LNA) gapmer-mediated PVT1 knockdown. RNA sequencing analysis was conducted to identify genes and processes regulated by PVT1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified PVT1 as a lncRNA upregulated in cSCC in situ and cSCC, associated with the malignant phenotype of cSCC. We showed that the expression of PVT1 in cSCC was regulated by MYC. Both CRISPR-Cas9 deletion of the entire PVT1 locus and LNA gapmer-mediated knockdown of PVT1 transcript impaired the malignant behaviour of cSCC cells, suggesting that PVT1 is an oncogenic transcript in cSCC. Furthermore, knockout of PVT1 exon 2 inhibited cSCC tumour growth both in vivo and in vitro, demonstrating that exon 2 is a critical element for the oncogenic role of PVT1. Mechanistically, we showed that PVT1 was localized in the cell nucleus and its deletion resulted in cellular senescence, increased cyclin-dependent kinase inhibitor 1 (p21\/CDKN1A) expression and cell cycle arrest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study revealed a previously unrecognized role for exon 2 of PVT1 in its oncogenic role and that PVT1 suppresses cellular senescence in cSCC. PVT1 may be a potential biomarker and therapeutic target in cSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljad419","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T09:25:45Z","timestamp":1698744345000},"page":"415-426","source":"Crossref","is-referenced-by-count":18,"title":["Long noncoding RNA plasmacytoma variant translocation\u00a01 is overexpressed in cutaneous squamous\u00a0cell carcinoma and exon 2 is critical for its\u00a0oncogenicity"],"prefix":"10.1093","volume":"190","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology (IMBIM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology (IMBIM)"},{"name":"Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal Das","family":"Mahapatra","sequence":"additional","affiliation":[{"name":"Dermatology and Venereology Division, Department of Medicine Solna"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilvi","family":"Riihil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"FICAN West Cancer Research Laboratory, University of Turku and Turku University Hospital , Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Knuutila","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"FICAN West Cancer Research Laboratory, University of Turku and Turku University Hospital , Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liisa","family":"Nissinen","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"FICAN West Cancer Research Laboratory, University of Turku and Turku University Hospital , Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lapins","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli-Matti","family":"K\u00e4h\u00e4ri","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"FICAN West Cancer Research Laboratory, University of Turku and Turku University Hospital , Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Homey","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Duesseldorf, Medical Faculty, Heinrich-Heine-University , D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enik\u00f6","family":"Sonkoly","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology (IMBIM)"},{"name":"Dermatology and Venereology Division, Department of Medicine Solna"},{"name":"Dermatology and Venereology, Department of Medical Sciences, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-1102","authenticated-orcid":false,"given":"Andor","family":"Pivarcsi","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology (IMBIM)"},{"name":"Dermatology and Venereology Division, Department of Medicine Solna"},{"name":"Dermatology and Venereology, Department of Medical Sciences, Uppsala University , Uppsala 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