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1.
Lab Invest ; 95(9): 1056-70, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26098000

RESUMO

The miR-19 family (miR-19a and miR-19b-1) are key oncogenic components of the miR-17-92 cluster. Overexpression of miR-19 is strongly associated with cancer invasion and metastasis, and poor prognosis of cancer patients. However, the underlying mechanisms remain largely unknown. In the present study, we found that enforced expression of miR-19 including miR-19a and miR-19b-1 triggered epithelial-mesenchymal transition (EMT) of lung cancer cells A549 and HCC827 as shown by mesenchymal-like morphological conversion, downregulation of epithelial proteins (e.g., E-cadherin, ZO-1 (zona occludens 1), and α-catenin), upregulation of mesenchymal proteins (e.g., vimentin, fibronectin 1, N-cadherin, and snail1), formation of stress fibers, and reduced cell adhesion. In addition, enhanced migration and invasion were observed in the cancer cells A549 and HCC827 undergoing EMT. In contrast, silencing of endogenous miR-19 reversed EMT and reduced the migration and invasion abilities of A549 and HCC827 cells. DNA microarray results revealed significant changes of the expression of genes related to EMT, migration, and metastasis of miR-19-expressing A549 cells. Moreover, siRNA-mediated knockdown of PTEN, a target of miR-19, also resulted in EMT, migration, and invasion of A549 and HCC827 cells, suggesting that PTEN is involved in miR-19-induced EMT, migration and invasion of lung cancer cells. Furthermore, lung cancer cells undergoing EMT induced by miR-19 demonstrated reduced proliferation in vitro and in vivo, and enhanced resistance to apoptosis caused by TNF-α. Taken together, these findings suggest that miR-19 triggers EMT, which has an important role in the invasion and migration of lung cancer cells, accompanied by the reduced proliferation of cells.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Pulmonares/fisiopatologia , MicroRNAs/metabolismo , Animais , Antígenos CD/metabolismo , Western Blotting , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Luciferases , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Interferência de RNA , Fatores de Transcrição da Família Snail , Sais de Tetrazólio , Tiazóis , Fatores de Transcrição/metabolismo , Ensaio Tumoral de Célula-Tronco , Vimentina/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , alfa Catenina/metabolismo
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