Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer

Background An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional t...

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Vydáno v:BMC cancer Ročník 16; číslo 1; s. 102
Hlavní autoři: Schmid, Gabriel, Notaro, Sara, Reimer, Daniel, Abdel-Azim, Samira, Duggan-Peer, Michaela, Holly, Jessica, Fiegl, Heidi, Rössler, Julia, Wiedemair, Annemarie, Concin, Nicole, Altevogt, Peter, Marth, Christian, Zeimet, Alain Gustave
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 15.02.2016
BioMed Central Ltd
Springer Nature B.V
Témata:
Aged
Analysis
Biomedical and Life Sciences
Biomedicine
Cancer Research
DNA Methylation - genetics
Female
Gene expression
Gene Expression Regulation, Neoplastic - genetics
Gene Silencing
Health Promotion and Disease Prevention
Humans
Medicine/Public Health
Methylation
MicroRNAs - analysis
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
Oncology
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - mortality
Ovary - chemistry
Ovary - metabolism
Promoter Regions, Genetic - genetics
Research Article
Risk factors
Surgical Oncology
Survival Analysis
Tissue Array Analysis
Translational oncology
Epigenetics
Promotor hypermethylation
Gene-silencing
miR-34a
Ovarian cancer
ISSN:1471-2407, 1471-2407
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Shrnutí:Background An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes. Methods One hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene-specific DNA methylation was evaluated with MethyLight technique. Results Significantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium ( p =  0.002). The expression of miR-34a was found lower in type II than in type I cancers ( p =  0.037), in p53 mutated as compared to p53 wild type cancers ( p =  0.003) and in high grade compared to in low grade cancers ( p =  0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS ( p =  0.039) and OS ( p =  0.018). In serous cancers low miR-34a levels showed a worse OS confirmed also in multivariate analysis ( p =  0.022). miR-34a promoter methylation was found higher in type II cancers than in type I ( p =  0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples ( p =  0.05). Conclusion We demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor-suppressive character of miR-34a in ovarian cancer.
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ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-016-2135-2