論文 - 詳細
| RRC ID | 58596 |
|---|---|
| 著者 | Gomaa A, Peng D, Chen Z, Soutto M, Abouelezz K, Corvalan A, El-Rifai W. |
| タイトル | Epigenetic regulation of AURKA by miR-4715-3p in upper gastrointestinal cancers. |
| ジャーナル | Sci Rep |
| Abstract |
Aurora kinase A (AURKA) is frequently overexpressed in several cancers. miRNA sequencing and bioinformatics analysis indicated significant downregulation of miR-4715-3p. We found that miR-4715-3p has putative binding sites on the 3UTR region of AURKA. Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Luciferase reporter assays confirmed binding of miR-4715-3p on the 3UTR region of AURKA. miR-4715-3p mediated a reduction in AURKA levels leading to G2/M delay, chromosomal polyploidy, and cell death. We also detected a remarkable decrease in GPX4, an inhibitor of ferroptosis, with an increase in cleaved PARP and caspase-3. Inhibition of AURKA using siRNA produced similar results, suggesting a possible link between AURKA and GPX4. Analysis of UGC samples and cell models demonstrated increased methylation levels of several CpG nucleotides upstream of miR-4715-3p. 5-Aza-2'-deoxycytidine induced demethylation of several CpG nucleotides, restoring miR-4715-3p expression, leading to downregulation of AURKA. In conclusion, our data identified a novel epigenetic mechanism mediating silencing of miR-4715-3p and induction of AURKA in UGCs. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis. |
| 巻・号 | 9(1) |
| ページ | 16970 |
| 公開日 | 2019-11-18 |
| DOI | 10.1038/s41598-019-53174-6 |
| PII | 10.1038/s41598-019-53174-6 |
| PMID | 31740746 |
| PMC | PMC6861278 |
| MeSH | 3' Untranslated Regions Antineoplastic Agents / pharmacology Aurora Kinase A / genetics* Cisplatin / pharmacology DNA Methylation Epigenesis, Genetic* Gastrointestinal Neoplasms / genetics* Gene Expression Regulation, Neoplastic Humans Kaplan-Meier Estimate MicroRNAs / genetics* Phospholipid Hydroperoxide Glutathione Peroxidase / genetics Polyploidy Stomach Neoplasms / drug therapy Stomach Neoplasms / genetics Stomach Neoplasms / mortality Stomach Neoplasms / pathology Upper Gastrointestinal Tract |
| IF | 3.998 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |