Down-regulation of miR-145 and miR-143 might be associated with DNA methyltransferase 3B overexpression and worse prognosis in endometrioid carcinomas.
The aim of this study was to determine the clinicopathologic significance of miR-145 and miR-143 down-regulation in endometrial cancers. The microRNA profiles were analyzed by microRNA microarray. The expression levels of miR-145 and miR-143 in 73 endometrial cancers were further determined by quantitative real-time polymerase chain reaction. Potential targets of miR-145/143 were defined. The status of DNA methyltransferase 3B (DNMT3B), mutL homologs 1, and phosphatase and tensin homolog was assessed using immunohistochemistry. miR-145 and miR-143 frequently co-down-regulated in endometrial cancers, but the expression levels varied greatly between endometrioid carcinomas (ECs) and non-ECs (NECs); they were significantly lower in ECs than in NECs (P < .05). DNMT3B was defined as a potential target of miR-145/143 by Internet algorithms. In ECs, DNMT3B overexpression occurred more often in the miR-145 and miR-143 down-regulation subgroups, and the correlation between DNMT3B and miR-145 status reached statistical significance (P = .021), whereas such phenomena were not present in NECs (P > .05). In univariate analysis, the combination of DNMT3B overexpression and miR-145 or miR-143 down-regulation was more powerful in predicting shorter survival (P < .05) than use of the biomarkers individually (P > .05). In multivariate analysis, such combination was not an independent predictor of disease-free survival (P > .05). Our findings suggest that the target and function of miR-145 and miR-143 may differ in ECs versus NECs. DNMT3B might be a potential target of miR-145 and miR-143 in ECs. Furthermore, the combined miR-145 or miR-143 and DNMT3B status may have a prognostic impact on ECs.
Department of Pathology, The Peking University, First Hospital, Beijing 100034, China.
Xiaoming
X
Zhang
Ying
Y
Dong
Hongjuan
H
Ti
Jing
J
Zhao
Ying
Y
Wang
Ting
T
Li
Bo
B
Zhang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D015854:Up-Regulation; D000097584:DNA Methyltransferase 3B
D048868:Adaptor Proteins, Signal Transducing; D004248:DNA (Cytosine-5-)-Methyltransferases; D035683:MicroRNAs; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D012334:RNA, Neoplasm; D000097584:DNA Methyltransferase 3B; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; C501486:MLH1 protein, human; C494929:PTEN protein, human
DNA methyltransferase 3B; DNA mismatch repair; DNMT3B; ECs; Endometrioid carcinomas; FFPE; HER-2; IHC; IRS; LOH; MMR; MicroRNA; NECs; Non-endometrioid carcinomas; PTEN; Prognosis; RQ; TLDA; TaqMan low-density arrays; endometrioid carcinomas; formalin-fixed, paraffin-embedded; hMLH1; human MutL homologs 1; human epidermal growth factor receptor 2; immunohistochemistry; immunoreactive score; loss of heterozygosity; miR (miRNA); miR-143; miR-145; microRNA; non-endometrioid carcinomas; phosphatase and tensin homolog; qRT-PCR; quantitative real-time polymerase chain reaction; relative quantity