Molecular bases of aberrant miR-182 expression in ovarian cancer.
The molecular bases of miR-182 deregulation in epithelial ovarian cancers (EOCs) remain unknown and its diagnostic or prognostic role in EOCs is still unclear. We performed miR-182 expression analysis using a microarray approach and real-time PCR (qPCR). We also used array comparative genomic hybridization and methylated DNA immunoprecipitation to study copy number changes and methylation aberrations within coding locus/promoter sequences of miR-182 in EOC tissues, respectively. We have found that miR-182 expression is significantly increased in EOC (P < 0.00001) and that higher miR-182 expression in EOC is linked with significantly shorter overall survival (P = 0.026). The methylation of miR-182 promoter was significantly associated with lower miR-182 expression in EOC tissues (P = 0.045). miR-182 over-expression is connected with copy number (CN) gains of this miRNA coding sequences in EOC (P = 0.002), and the number of PRDM5 copies is significantly and inversely correlated with miR-182 expression evaluated by qPCR (R = -0.615, P = 0.009). We conclude that the aberrant miR-182 expression in EOC may be due to CN gains within its coding locus. The miR-182 promoter is rarely methylated in EOC, and its methylation status is associated with lower miR-182 expression. Deletion of the PRDM5 locus may play a supportive role in miR-182 overexpression in EOC. miR-182 is an unfavorable prognostic factor in EOC. © 2016 Wiley Periodicals, Inc.
Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland. barbara.marzec@umlub.pl.
Barbara
B
Marzec-Kotarska
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Marek
M
Cybulski
Second Department of Gynecological Oncology, St. John's Cancer Oncology Center Lublin, Lublin, Poland.
Józef Czesław
JC
Kotarski
Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, Gdańsk, Poland.
Anna
A
Ronowicz
1 st Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin, Poland.
Rafał
R
Tarkowski
1 st Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin, Poland.
Grzegorz
G
Polak
Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland.
Halina
H
Antosz
Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, Gdańsk, Poland.
Arkadiusz
A
Piotrowski
1 st Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin, Poland.
Jan
J
Kotarski
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C487762:PRDM5 protein, human; D014157:Transcription Factors