Details

Autor(en) / Beteiligte

• NADAL, Ernest
• GUOAN CHEN
• ESCOBAR, Ignacio
• MOYA, Juan
• CHANG, Andrew C
• CARDENAL, Felipe
• CAPELLA, Gabriel
• BEER, David G
• GALLEGOS, Marc
• LIN LIN
• FERRER-TORRES, Daysha
• TRUINI, Anna
• ZHUWEN WANG
• LIN, Jules
• REDDY, Rishindra M
• LLATJOS, Roger

Titel

Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma

Ist Teil von

• Clinical cancer research, 2013-12, Vol.19 (24), p.6842-6852

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2013

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The microRNA-34b/c (miR-34b/c) is considered a tumor suppressor in different tumor types and a transcriptional target of TP53. The main objectives of this study were to investigate the clinical implications of miR-34b/c methylation in patients with early-stage lung adenocarcinoma and to determine the functional role of miR-34b/c re-expression in lung adenocarcinoma cell lines. Aberrant methylation and expression of miR-34b/c were assessed in 15 lung adenocarcinoma cell lines and a cohort of 140 early-stage lung adenocarcinoma. Lung adenocarcinoma cell lines were transfected with miR-34b/c and the effects upon cell proliferation, migration, invasion, and apoptosis were investigated. Aberrant methylation of miR-34b/c was detected in 6 (40%) of 15 lung adenocarcinoma cell lines and 64 of 140 (46%) primary lung adenocarcinoma. Expression of miR-34b/c was significantly reduced in all methylated cell lines and primary tumors, especially with TP53 mutations. Patients with increased miR-34b/c methylation had significantly shorter disease-free and overall survival as compared to patients with unmethylated or low level of miR-34b/c methylation. Ectopic expression of miR-34b/c in lung adenocarcinoma cell lines decreased cell proliferation, migration, and invasion. Epigenetic inactivation of miR-34b/c by DNA methylation has independent prognostic value in patients with early-stage lung adenocarcinoma. Reexpression of miR-34b/c leads to a less aggressive phenotype in lung adenocarcinoma cell lines.