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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 February 2016
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| In: |
BMC cancer
Year: 2016, Volume: 16 |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-016-2135-2 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1186/s12885-016-2135-2 Verlag, Volltext: https://doi.org/10.1186/s12885-016-2135-2 
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| Author Notes: | Gabriel Schmid, Sara Notaro, Daniel Reimer, Samira Abdel-Azim, Michaela Duggan-Peer, Jessica Holly, Heidi Fiegl, Julia Rössler, Annemarie Wiedemair, Nicole Concin, Peter Altevogt, Christian Marth and Alain Gustave Zeimet |
| Summary: | 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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| Item Description: | Gesehen am 07.02.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-016-2135-2 |