論文 - 詳細
| RRC ID | 73799 |
|---|---|
| 著者 | Wang Z, Xia X, Li J, Igaki T. |
| タイトル | Tumor elimination by clustered microRNAs miR-306 and miR-79 via noncanonical activation of JNK signaling. |
| ジャーナル | Elife |
| Abstract |
JNK signaling plays a critical role in both tumor promotion and tumor suppression. Here, we identified clustered microRNAs (miRNAs) miR-306 and miR-79 as novel tumor-suppressor miRNAs that specifically eliminate JNK-activated tumors in Drosophila. While showing only a slight effect on normal tissue growth, miR-306 and miR-79 strongly suppressed growth of multiple tumor models, including malignant tumors caused by Ras activation and cell polarity defects. Mechanistically, these miRNAs commonly target the mRNA of an E3 ubiquitin ligase ring finger protein 146 (RNF146). We found that RNF146 promotes degradation of tankyrase (Tnks), an ADP-ribose polymerase that promotes JNK activation in a noncanonical manner. Thus, downregulation of RNF146 by miR-306 and miR-79 leads to hyper-enhancement of JNK activation. Our data show that, while JNK activity is essential for tumor growth, elevation of miR-306 or miR-79 overactivate JNK signaling to the lethal level via noncanonical JNK pathway and thus eliminate tumors, providing a new miRNA-based strategy against cancer. |
| 巻・号 | 11 |
| 公開日 | 2022-10-12 |
| DOI | 10.7554/eLife.77340 |
| PII | 77340 |
| PMID | 36222503 |
| PMC | PMC9612915 |
| MeSH | Adenosine Diphosphate Ribose Genes, Tumor Suppressor Humans MAP Kinase Signaling System MicroRNAs* / genetics Neoplasms* / genetics |
| IF | 7.08 |
| 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 | 5 |
| 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 | |
| ショウジョウバエ | |