RESUMO
The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We report here that silencing SMURF2 (SMAD specific E3 ubiquitin protein ligase 2) promoted EMT in HPDE6c7 normal pancreas cells and overexpression of SMURF2 inhibited TGF-ß-mediated EMT in the cells. Subsequent studies showed that SMURF2 was downregulated in pancreatic cancer tissues and it promoted mesenchymal-epithelial transition (MET) in pancreatic cancer cells as well as its expression negatively associated with gemcitabine-resistance, but it did not alter cell viability, cell cycle and cell senescence. In addition, we demonstrated that miR15b degraded SMURF2 and its overexpression promoted EMT in pancreatic cancer, and its expression was associated with metastasis in the disease. Elucidating molecular mechanism of EMT in pancreatic cancer not only will help us to further understand the pathogenesis and progression of the disease, but also offers new targets for effective therapies.
Assuntos
Transição Epitelial-Mesenquimal , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica , Neoplasias Pancreáticas/metabolismo , Regiões Promotoras Genéticas , Fator de Crescimento Transformador beta/farmacologia , GencitabinaRESUMO
Thyroid cancer develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Elucidating molecular mechanism of the disease will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In this study, we found that MRTF-A expression was upregulated in metastatic anaplastic thyroid cancer tissues, compared with primary cancer tissues and it promoted metastasis-relevant traits in vitro. miR-206 was negatively associated with metastasis in anaplastic cancer and it degraded MRTF-A by targeting its 3'-UTR in ARO anaplastic thyroid cancer cells. In addition, miR-206 overexpression inhibited invasion and migration and silencing miR-206-promoted migration and invasion in the cells. Important, restoration of MRTF-A could abrogate miR-206-mediated migration and invasion regulation. Thus, we concluded that miR-206 inhibited invasion and metastasis by degrading MRTF-A in anaplastic thyroid cancer.