MicroRNA-203 Inversely Correlates with Differentiation Grade, Targets c-MYC, and Functions as a Tumor Suppressor in cSCC.
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.
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
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Regulación Neoplásica de la Expresión Génica
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Genes myc
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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