title: MicroRNA-34b functions as a potential tumor suppressor in endometrial serous adenocarcinoma.
abstract: Endometrial serous adenocarcinoma (ESC) is aggressive and carries a poor prognosis. p53 is frequently mutated in ESC. microRNAs (miRNAs) are a direct p53 target and have been implicated in cancer cell behavior. In this study, we compared miRNA expression levels in ESC with the levels in endometrial endometrioid adenocarcinoma (EEC) and normal endometria. Six miRNAs were identified as having aberrant down-regulation specific to ESC with miR-34b being most pronounced. miR-34b was found to have promoter hypermethylation, which when reversed, restored miR-34b expression in the cell lines treated with 5-aza-2' deoxycytidine (DAC). Ectopic expression of miR-34b in turn inhibited cell growth, migration and most notably invasion. Our findings suggest a relationship among p53 mutation, miR-34b promoter methylation and tumor cell behavior. These effects are likely mediated by the downstream target of miR-34b, the proto-oncogene mesenchymal-epithelial transition factor (MET), a known prognostic factor in endometrial carcinomas. The expression of MET was reduced following the restoration of miR-34b in cell lines. In summary, our data suggest that miR-34b plays a role in the molecular pathogenesis of endometrial cancer.
authors: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Eri
authors: E
authors: Hiroki
authors: Fumihiko
authors: F
authors: Suzuki
authors: Jun-Ichi
authors: J
authors: Akahira
authors: Satoru
authors: S
authors: Nagase
authors: Kiyoshi
authors: K
authors: Ito
authors: Jun-Ichi
authors: J
authors: Sugawara
authors: Yasuhiro
authors: Y
authors: Miki
authors: Takashi
authors: T
authors: Suzuki
authors: Hironobu
authors: H
authors: Sasano
authors: Nobuo
authors: N
authors: Yaegashi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000715470:MAS1 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D000077209:Decitabine; D001374:Azacitidine