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Int J Cancer ; 146(2): 521-530, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31403184


It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/genética , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/genética , Taxa de Sobrevida , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia
Ann Diagn Pathol ; 14(4): 264-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20637432


Most teratomas involving the thyroid gland are benign and occur in children. However, the adult cases reported are mostly malignant. Many of the cases previously described in the medical literature have fatal outcome because of spread of the tumor refractory to treatment. We report a case of primary malignant teratoma of the thyroid in a 38-year-old pregnant black woman. She was treated with a combination of surgery, and postoperative chemotherapy with good initial response.

Complicações Neoplásicas na Gravidez/patologia , Teratoma/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina , Cisplatino , Terapia Combinada , Etoposídeo , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/cirurgia , Teratoma/tratamento farmacológico , Teratoma/cirurgia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia