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PTENP1-AS contribut...
PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma
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- Vidarsdottir, Linda (author)
- Karolinska Institute
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- Azimi, Alireza (author)
- Karolinska Institute
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- Das, Ishani (author)
- Karolinska Institute
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- Sigvaldadottir, Ingibjorg (author)
- Karolinska Institute
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- Suryo Rahmanto, Aldwin (author)
- Karolinska Institute
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- Petri, Andreas (author)
- Aalborg University
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- Kauppinen, Sakari (author)
- Aalborg University
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- Ingvar, Christian (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups
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- Jönsson, Göran (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Olsson, Håkan (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Frostvik Stolt, Marianne (author)
- Karolinska Institute
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- Tuominen, Rainer (author)
- Karolinska Institute
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- Sangfelt, Olle (author)
- Karolinska Institutet,Karolinska Institute
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- Pokrovskaja Tamm, Katja (author)
- Karolinska Institutet,Karolinska Institute
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- Hansson, Johan (author)
- Karolinska Institutet,Karolinska Institute
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- Grandér, Dan (author)
- Karolinska Institute
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- Egyházi Brage, Suzanne (author)
- Karolinska Institutet,Karolinska Institute
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- Johnsson, Per (author)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2021-05-26
- 2021
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Abstract
Subject headings
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- BRAF inhibitors (BRAFi) selectively target oncogenic BRAFV600E/K and are effective in 80% of advanced cutaneous malignant melanoma cases carrying the V600 mutation. 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 PTEN is negatively regulated by the PTEN pseudogene antisense RNA, PTENP1-AS, and here we investigated the impact of this transcript on clinical outcome and BRAFi resistance in melanoma. We observed that increased expression levels of PTENP1-AS in BRAFi resistant cells associated with enrichment of EZH2 and H3K27me3 at the PTEN promoter, consequently reducing the expression levels of PTEN. Further, we showed that targeting of the PTENP1-AS transcript sensitized resistant cells to BRAFi treatment and that high expression of PTENP1-AS in stage III melanoma correlated with poor survival. Collectively, the data presented here show that PTENP1-AS is a promising target for re-sensitizing cells to BRAFi and also a possible prognostic marker for clinical outcome in stage III melanoma.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Vidarsdottir, Li ...
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Azimi, Alireza
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Das, Ishani
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Sigvaldadottir, ...
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Suryo Rahmanto, ...
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Petri, Andreas
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show more...
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Kauppinen, Sakar ...
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Ingvar, Christia ...
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Jönsson, Göran
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Olsson, Håkan
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Frostvik Stolt, ...
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Tuominen, Rainer
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Sangfelt, Olle
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Pokrovskaja Tamm ...
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Hansson, Johan
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Grandér, Dan
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Egyházi Brage, S ...
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Johnsson, Per
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Scientific Repor ...
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Lund University
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Karolinska Institutet