Abstract | BACKGROUND: RESULTS: In this work, a negative correlation between DDR1 and a tumor suppressor miRNA, miR-199a-3p, was observed in ovarian cancer tissues. Furthermore, in vitro experimental results confirmed that miR-199a-3p decreased the expression of DDR1 via targeting the 3'UTR of DDR1 mRNA. To explore the mechanisms for miR-199a-3p silence in ovarian cancer, the methylation status of the miR-199a promoter was analyzed in ovarian epithelial or cancer cells by methylation-specific PCR and bisulphite sequencing. As expected, the miR-199a promoter was hypermethylated in ovarian cancer cells but not in normal ovarianepithelial cells. Interestingly, knockdown of DNA methyltransferase 3A (DNMT3A) notably increased miR-199a-3p level and then attenuated the expression of DDR1 in ovarian cancer cells, which suggested that DNMT3A was responsible for the miR-199a promoter hypermethylation. Phenotype experiments showed that overexpression of miR-199a-3p significantly impaired the migratory, invasive, and tumorigenic capabilities of ovarian cancer cells as well as enhanced cisplatin resistance through inhibiting DDR1 expression. CONCLUSION: These findings demonstrate a critical role of miR-199a-3p/DDR1 pathway in ovarian cancer development.
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Authors | Yuao Deng, Fang Zhao, Liu Hui, Xiuyun Li, Danyu Zhang, Wang Lin, Zhiqiang Chen, Yingxia Ning |
Journal | Journal of ovarian research
(J Ovarian Res)
Vol. 10
Issue 1
Pg. 50
(Jul 25 2017)
ISSN: 1757-2215 [Electronic] England |
PMID | 28743276
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- DNMT3A protein, human
- MicroRNAs
- mirn199 microRNA, human
- DNA Methyltransferase 3A
- DDR1 protein, human
- Discoidin Domain Receptor 1
- Cisplatin
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Topics |
- Aged
- Antineoplastic Agents
(pharmacology)
- Cell Line
- Cell Line, Tumor
- Cell Movement
- Cell Survival
(drug effects)
- Cisplatin
(pharmacology)
- DNA Methylation
- DNA Methyltransferase 3A
- Discoidin Domain Receptor 1
(genetics, metabolism)
- Drug Resistance, Neoplasm
(drug effects, genetics)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- MicroRNAs
(genetics)
- Ovarian Neoplasms
(genetics, metabolism, pathology)
- Promoter Regions, Genetic
- Wound Healing
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