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Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33006362

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related mortality globally. However, the mechanism underlying NSCLC is not fully understood. Here, we investigated the role of cancer-related regulator of actin dynamics (CRAD) in NSCLC. We showed that CRAD was up-regulated in human NSCLC tissues and lung cancer cell lines. Lentivirus-mediated knockdown of CRAD repressed the proliferation and colony growth of A549 and H1299 cells. Apoptosis was enhanced by CRAD silencing in both cells, implicating that CRAD might maintain the survival of lung cancer cells. Microarray and bioinformatic assay revealed that CRAD directly or indirectly regulated diverse genes, including those involved in cell cycle and DNA damage repair. qRT-PCR and Western blot results confirmed the dysregulated genes as shown in microarray analysis. Claudin 4 was up-regulated in CRAD silenced A549 cells. The knockdown of Claudin 4 blocked the effects of CRAD on the expression of cell cycle and apoptosis effectors and enhanced the viability of A549 cells with CRAD down-regulation. Taken together, our findings demonstrate that CRAD acts as an oncogene in NSCLC at least partly through repressing Claudin 4.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Claudina-4/genética , Neoplasias Pulmonares/patologia , Proteínas dos Microfilamentos/metabolismo , Células A549 , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Ciclo Celular/genética , Proliferação de Células/genética , Biologia Computacional , Dano ao DNA , Reparo do DNA/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Proteínas dos Microfilamentos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/genética , Regulação para Cima
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