Cancer letters · 2014
miR-145, targeting high-mobility group A2, is a powerful predictor of patient outcome in ovarian carcinoma.
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Kim Tae Hoen, Song Ji-Ye, Park Hyun, Jeong Ju-Yeon, Kwon A-Young, Heo Jin Hyung, Kang Haeyoun, Kim Gwangil, An Hee Jung
Аннотация
MicroRNA-145 (miR-145) expression is downregulated in several human cancers, but its clinical and functional relevance to ovarian carcinoma has not yet been elucidated. This study addressed the hypothesis that miR-145 serves as a prognostic biomarker and a tumor suppressor that regulates the expression of high-mobility group A2 (HMGA2) oncoprotein in ovarian cancer. Here, we found that low miR-145 expression and HMGA2 overexpression determined by qRT-PCR and immunohistochemistry significantly correlated with advanced stage, lymph node involvement, and distant metastasis in 74 ovarian carcinomas. Low miR-145 expression significantly correlated with tumor recurrence and worse overall survival (HR=8.62, P = 0.039). Transfection of pre-miR-145 resulted in reduced cell growth and migration, and increased apoptosis of ovarian cancer cells by TUNEL, colony forming, and cell migration assays. MiR-145 was found to directly target HMGA2 by luciferase assay and Western blotting. Our findings suggest that miR-145 functions as a tumor suppressor in ovarian cancer and directly targets HMGA2 oncoprotein. Low miR-145 and high HMGA2 expressions are potential biomarkers of poor prognosis of ovarian carcinoma and miR-145 is the more powerful predictor of patient outcome.
Предметные рубрики MeSH
AdultAgedAged, 80 and overApoptosisBlotting, WesternCell ProliferationFemaleGene Expression Regulation, NeoplasticHMGA2 ProteinHumansImmunoenzyme TechniquesLymphatic MetastasisMicroRNAsMiddle AgedNeoplasm GradingNeoplasm Recurrence, LocalNeoplasm StagingOvarian NeoplasmsPrognosisRNA, MessengerReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSurvival RateTissue Array AnalysisTumor Cells, CulturedTumor Stem Cell AssayWound Healing