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Artif Cells Nanomed Biotechnol ; 46(8): 1754-1762, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29073835

RESUMO

Oral cancer remains a major public concern with considerable socioeconomic impact in the world, especially in southeast Asia. Despite substantial advancements have been made in treating oral cancer, the five-year survival rate for OSCC remained undesirable, and 35-55% patients developed recurrence within two years even with multimodality therapeutic strategies. Hence, identification of novel biomarkers for diagnosis and evaluating clinical outcome is of vital importance. MicroRNAs are 22-24 nt non-coding RNAs that could bind to 3' UTR of target mRNAs, thereby inducing degradation of mRNA or inhibiting translation. Due to its implication in regulation of post-transcriptional processes, the role of miRNAs in malignancies has been extensively studied, among which the discovery of functional miR-9 in oral squamous cell carcinoma (OSCC) remained to be elucidated. We first demonstrated that miR-9 was down-regulated in 21 OSCC patients, and we further found that forced expression of miR-9 could result in deterred cell proliferation and decreased ability to migrate and form colonies. Flow cytometry displayed cell-cycle arrested at G0/G1 phase. We next used Targetscan to predict target genes of miR-9. CDK6, a protein highly implicated in cell cycle control, was chosen for verification. Down-regulation of CDK6 and Cyclin D1 in Tca8113 transfected with miR-9 mimics indicate that the complex formed by both proteins may be the effector of the antiproliferative function of miR-9 in OSCCs. Considering small molecules are developed to target CDK4/6, our finding may provide valuable scientific evidence for research and development of therapies and diagnostic methodology in OSCCs.


Assuntos
Apoptose , Carcinoma de Células Escamosas/metabolismo , Pontos de Checagem do Ciclo Celular , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , MicroRNAs/biossíntese , Proteínas de Neoplasias/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Neoplasias da Língua/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Neoplasias da Língua/genética , Neoplasias da Língua/patologia
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