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However, the development of drug resistance limits their clinical efficacy. Better characterization of the underlying molecular processes is needed to further improve treatments. We previously demonstrated that transcription of\n                    <jats:italic>PTEN<\/jats:italic>\n                    is negatively regulated by the\n                    <jats:italic>PTEN<\/jats:italic>\n                    pseudogene antisense RNA,\n                    <jats:italic>PTENP1-AS<\/jats:italic>\n                    , and here we investigated the impact of this transcript on clinical outcome and BRAFi resistance in melanoma. We observed that increased expression levels of\n                    <jats:italic>PTENP1-AS<\/jats:italic>\n                    in BRAFi resistant cells associated with enrichment of EZH2 and H3K27me3 at the\n                    <jats:italic>PTEN<\/jats:italic>\n                    promoter, consequently reducing the expression levels of\n                    <jats:italic>PTEN<\/jats:italic>\n                    . Further, we showed that targeting of the\n                    <jats:italic>PTENP1-AS<\/jats:italic>\n                    transcript sensitized resistant cells to BRAFi treatment and that high expression of\n                    <jats:italic>PTENP1-AS<\/jats:italic>\n                    in stage III melanoma correlated with poor survival. Collectively, the data presented here show that\n                    <jats:italic>PTENP1-AS<\/jats:italic>\n                    is a promising target for re-sensitizing cells to BRAFi and also a possible prognostic marker for clinical outcome in stage III melanoma.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-89389-9","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T06:04:00Z","timestamp":1622009040000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma"],"prefix":"10.1038","volume":"11","author":[{"given":"Linda","family":"Vidarsdottir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Azimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishani","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingibjorg","family":"Sigvaldadottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldwin","family":"Suryo Rahmanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Petri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakari","family":"Kauppinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ingvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"J\u00f6nsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Frostvik Stolt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Tuominen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"Sangfelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Pokrovskaja Tamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Grand\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Egyh\u00e1zi Brage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Johnsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"89389_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766","author":"H Davies","year":"2002","unstructured":"Davies, H. et al. 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Activities of multiple cancer-related pathways are associated with BRAF mutation and predict the resistance to BRAF\/MEK inhibitors in melanoma cells. Cell Cycle https:\/\/doi.org\/10.4161\/cc.26971 (2014).","journal-title":"Cell Cycle"},{"key":"89389_CR5","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6548","author":"DG Roller","year":"2016","unstructured":"Roller, D. G. et al. Combinatorial drug screening and molecular profiling reveal diverse mechanisms of intrinsic and adaptive resistance to BRAF inhibition in V600E BRAF mutant melanomas. Oncotarget https:\/\/doi.org\/10.18632\/oncotarget.6548 (2016).","journal-title":"Oncotarget"},{"key":"89389_CR6","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2954","author":"KHT Paraiso","year":"2011","unstructured":"Paraiso, K. H. T. et al. PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-2954 (2011).","journal-title":"Cancer Res."},{"key":"89389_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-9-r51","author":"B Pei","year":"2012","unstructured":"Pei, B. et al. The GENCODE pseudogene resource. Genome Biol. https:\/\/doi.org\/10.1186\/gb-2012-13-9-r51 (2012).","journal-title":"Genome Biol."},{"key":"89389_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2516","author":"P Johnsson","year":"2013","unstructured":"Johnsson, P. et al. A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat. Struct. Mol. Biol. https:\/\/doi.org\/10.1038\/nsmb.2516 (2013).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"89389_CR9","doi-asserted-by":"publisher","DOI":"10.4161\/trns.1.3.13332","author":"PG Hawkins","year":"2010","unstructured":"Hawkins, P. G. & Morris, K. V. Transcriptional regulation of Oct4 by a long non-coding RNA antisense to Oct4-pseudogene 5. 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