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MicroRNA-203 Inversely Correlates with Differentiation Grade, Targets c-MYC, and Functions as a Tumor Suppressor in cSCC.
Lohcharoenkal, Warangkana; Harada, Masako; Lovén, Jakob; Meisgen, Florian; Landén, Ning Xu; Zhang, Lingyun; Lapins, Jan; Mahapatra, Kunal Das; Shi, Hao; Nissinen, Liisa; Kähäri, Veli-Matti; Ståhle, Mona; Sonkoly, Enikö; Grandér, Dan; Arsenian-Henriksson, Marie; Pivarcsi, Andor.
Afiliación
  • Lohcharoenkal W; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Harada M; Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
  • Lovén J; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Meisgen F; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Landén NX; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Zhang L; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Lapins J; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Mahapatra KD; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Shi H; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Nissinen L; Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
  • Kähäri VM; Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
  • Ståhle M; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Sonkoly E; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Grandér D; Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
  • Arsenian-Henriksson M; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
  • Pivarcsi A; Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: Andor.Pivarcsi@ki.se.
J Invest Dermatol ; 136(12): 2485-2494, 2016 12.
Article en En | MEDLINE | ID: mdl-27452220
ABSTRACT
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer and a leading cause of cancer mortality among solid organ transplant recipients. MicroRNAs (miR) are short RNAs that regulate gene expression and cellular functions. Here, we show a negative correlation between miR-203 expression and the differentiation grade of cSCC. Functionally, miR-203 suppressed cell proliferation, cell motility, and the angiogenesis-inducing capacity of cSCC cells in vitro and reduced xenograft tumor volume and angiogenesis in vivo. Transcriptomic analysis of cSCC cells with ectopic overexpression of miR-203 showed dramatic changes in gene networks related to cell cycle and proliferation. Transcription factor enrichment analysis identified c-MYC as a hub of miR-203-induced transcriptomic changes in squamous cell carcinoma. We identified c-MYC as a direct target of miR-203. Overexpression of c-MYC in rescue experiments reversed miR-203-induced growth arrest in cSCC, which highlights the importance of c-MYC within the miR-203-regulated gene network. Together, miR-203 acts as a tumor suppressor in cSCC, and its low expression can be a marker for poorly differentiated tumors. Restoration of miR-203 expression may provide a therapeutic benefit, particularly in poorly differentiated cSCC.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_skin_diseases Asunto principal: Neoplasias Cutáneas / Carcinoma de Células Escamosas / Regulación Neoplásica de la Expresión Génica / Genes myc / MicroARNs Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: J Invest Dermatol Año: 2016 Tipo del documento: Article País de afiliación: Suecia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_skin_diseases Asunto principal: Neoplasias Cutáneas / Carcinoma de Células Escamosas / Regulación Neoplásica de la Expresión Génica / Genes myc / MicroARNs Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: J Invest Dermatol Año: 2016 Tipo del documento: Article País de afiliación: Suecia
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