Association of JAK/STAT genetic variants with cutaneous melanoma
BackgroundThe Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway regulates cutaneous melanoma (CM) development and progression. The JAK1, JAK2, and STAT3 proteins are encoded by polymorphic genes. This study aimed to verify whether single-nucleotid...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.943483/full |
| _version_ | 1828358677245984768 |
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| author | Gabriela Vilas Bôas Gomez Gustavo Jacob Lourenço Lummy Maria Oliveira Monteiro Rafael Silva Rocha Kimberly Anne McGrail Fernández Juan Angel Recio Caroline Torricelli Lilian Oliveira Coser Alexandre Leite Rodrigues Oliveira Juliana Carron Aparecida Machado Moraes Carmen Silvia Passos Lima Carmen Silvia Passos Lima |
| author_facet | Gabriela Vilas Bôas Gomez Gustavo Jacob Lourenço Lummy Maria Oliveira Monteiro Rafael Silva Rocha Kimberly Anne McGrail Fernández Juan Angel Recio Caroline Torricelli Lilian Oliveira Coser Alexandre Leite Rodrigues Oliveira Juliana Carron Aparecida Machado Moraes Carmen Silvia Passos Lima Carmen Silvia Passos Lima |
| author_sort | Gabriela Vilas Bôas Gomez |
| collection | DOAJ |
| description | BackgroundThe Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway regulates cutaneous melanoma (CM) development and progression. The JAK1, JAK2, and STAT3 proteins are encoded by polymorphic genes. This study aimed to verify whether single-nucleotide variants (SNVs) in JAK1 (c.1648+1272G>A, c.991-27C>T), JAK2 (c.-1132G>T, c.-139G>A), and STAT3 (c.*1671T>C, c.-1937C>G) altered the risk, clinicopathological aspects, and survival of CM patients as well as protein activity.MethodsCM patients (N = 248) and controls (N = 274) were enrolled in this study. Genotyping was performed by real-time polymerase chain reaction (PCR), and JAK1, JAK2, and STAT3 expression was assessed by quantitative PCR (qPCR). STAT3 c.-1937C>G SNV was investigated by luciferase, qPCR, western blot, apoptosis, and cell cycle assays in SKMEL-28 cells with CC or GG genotype.ResultsIndividuals with STAT3 c.*1671TT and c.-1937CC genotypes and TC haplotype of both SNVs were under about 2.0-fold increased risk of CM. Specific JAK1, JAK2, and STAT3 combined genotypes were associated with up to 4.0-fold increased risk of CM. Higher luciferase activity [4,013.34 vs. 2,463.32 arbitrary units (AU); p = 0.004], STAT3 expression by qPCR (649.20 vs. 0.03 AU; p = 0.003) and western blot (1.69 vs. 1.16 AU; p = 0.01), and percentage of cells in the S phase of the cell cycle (57.54 vs. 30.73%; p = 0.04) were more frequent in SKMEL-28 with STAT3 c.-1937CC than with GG genotype. CM cell line with CC genotype presented higher STAT3 protein levels than the one with GG genotype (1.93 versus 1.27 AU, p = 0.0027).ConclusionOur data present preliminary evidence that inherited abnormalities in the JAK/STAT pathway can be used to identify individuals at a high risk of CM, who deserve additional attention for tumor prevention and early detection. |
| first_indexed | 2024-04-14T03:33:19Z |
| format | Article |
| id | doaj.art-e0944b4ea6584aa6950d79f56be70ec6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T03:33:19Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-e0944b4ea6584aa6950d79f56be70ec62022-12-22T02:14:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.943483943483Association of JAK/STAT genetic variants with cutaneous melanomaGabriela Vilas Bôas Gomez0Gustavo Jacob Lourenço1Lummy Maria Oliveira Monteiro2Rafael Silva Rocha3Kimberly Anne McGrail Fernández4Juan Angel Recio5Caroline Torricelli6Lilian Oliveira Coser7Alexandre Leite Rodrigues Oliveira8Juliana Carron9Aparecida Machado Moraes10Carmen Silvia Passos Lima11Carmen Silvia Passos Lima12Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, BrazilLaboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, BrazilDepartment of Cellular and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, BrazilDepartment of Cellular and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, BrazilAnimal Models and Cancer Laboratory, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Barcelona, SpainAnimal Models and Cancer Laboratory, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Barcelona, SpainLaboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, BrazilLaboratory of Nerve Regeneration, Department of Structural and Functional Biology, Institute of Biology, University of Campinas, São Paulo, BrazilLaboratory of Nerve Regeneration, Department of Structural and Functional Biology, Institute of Biology, University of Campinas, São Paulo, BrazilLaboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, BrazilDepartment of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, University of Campinas, São Paulo, BrazilLaboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, BrazilDepartment of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, University of Campinas, São Paulo, BrazilBackgroundThe Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway regulates cutaneous melanoma (CM) development and progression. The JAK1, JAK2, and STAT3 proteins are encoded by polymorphic genes. This study aimed to verify whether single-nucleotide variants (SNVs) in JAK1 (c.1648+1272G>A, c.991-27C>T), JAK2 (c.-1132G>T, c.-139G>A), and STAT3 (c.*1671T>C, c.-1937C>G) altered the risk, clinicopathological aspects, and survival of CM patients as well as protein activity.MethodsCM patients (N = 248) and controls (N = 274) were enrolled in this study. Genotyping was performed by real-time polymerase chain reaction (PCR), and JAK1, JAK2, and STAT3 expression was assessed by quantitative PCR (qPCR). STAT3 c.-1937C>G SNV was investigated by luciferase, qPCR, western blot, apoptosis, and cell cycle assays in SKMEL-28 cells with CC or GG genotype.ResultsIndividuals with STAT3 c.*1671TT and c.-1937CC genotypes and TC haplotype of both SNVs were under about 2.0-fold increased risk of CM. Specific JAK1, JAK2, and STAT3 combined genotypes were associated with up to 4.0-fold increased risk of CM. Higher luciferase activity [4,013.34 vs. 2,463.32 arbitrary units (AU); p = 0.004], STAT3 expression by qPCR (649.20 vs. 0.03 AU; p = 0.003) and western blot (1.69 vs. 1.16 AU; p = 0.01), and percentage of cells in the S phase of the cell cycle (57.54 vs. 30.73%; p = 0.04) were more frequent in SKMEL-28 with STAT3 c.-1937CC than with GG genotype. CM cell line with CC genotype presented higher STAT3 protein levels than the one with GG genotype (1.93 versus 1.27 AU, p = 0.0027).ConclusionOur data present preliminary evidence that inherited abnormalities in the JAK/STAT pathway can be used to identify individuals at a high risk of CM, who deserve additional attention for tumor prevention and early detection.https://www.frontiersin.org/articles/10.3389/fonc.2022.943483/fullcutaneous melanomaJAK1JAK2STAT3genetic variantrisk |
| spellingShingle | Gabriela Vilas Bôas Gomez Gustavo Jacob Lourenço Lummy Maria Oliveira Monteiro Rafael Silva Rocha Kimberly Anne McGrail Fernández Juan Angel Recio Caroline Torricelli Lilian Oliveira Coser Alexandre Leite Rodrigues Oliveira Juliana Carron Aparecida Machado Moraes Carmen Silvia Passos Lima Carmen Silvia Passos Lima Association of JAK/STAT genetic variants with cutaneous melanoma Frontiers in Oncology cutaneous melanoma JAK1 JAK2 STAT3 genetic variant risk |
| title | Association of JAK/STAT genetic variants with cutaneous melanoma |
| title_full | Association of JAK/STAT genetic variants with cutaneous melanoma |
| title_fullStr | Association of JAK/STAT genetic variants with cutaneous melanoma |
| title_full_unstemmed | Association of JAK/STAT genetic variants with cutaneous melanoma |
| title_short | Association of JAK/STAT genetic variants with cutaneous melanoma |
| title_sort | association of jak stat genetic variants with cutaneous melanoma |
| topic | cutaneous melanoma JAK1 JAK2 STAT3 genetic variant risk |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.943483/full |
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