論文 - 詳細
| RRC ID | 38414 |
|---|---|
| 著者 | Tsuruta T, Kozaki K, Uesugi A, Furuta M, Hirasawa A, Imoto I, Susumu N, Aoki D, Inazawa J. |
| タイトル | miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. |
| ジャーナル | Cancer Res |
| Abstract |
The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer. |
| 巻・号 | 71(20) |
| ページ | 6450-62 |
| 公開日 | 2011-10-15 |
| DOI | 10.1158/0008-5472.CAN-11-0364 |
| PII | 0008-5472.CAN-11-0364 |
| PMID | 21868754 |
| MeSH | Adenocarcinoma / genetics Adenocarcinoma / metabolism* Carrier Proteins / metabolism Cell Line, Tumor Cell Proliferation / drug effects Chromosomes, Human, Pair 17 / genetics Coatomer Protein / genetics DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases / metabolism DNA Methylation* E2F3 Transcription Factor / metabolism Endometrial Neoplasms / genetics Endometrial Neoplasms / metabolism* Female Gene Silencing* Genes, Tumor Suppressor* Humans Introns MicroRNAs / genetics MicroRNAs / metabolism* Proto-Oncogene Proteins c-met / metabolism Rapamycin-Insensitive Companion of mTOR Protein |
| IF | 9.727 |
| 引用数 | 160 |
| WOS 分野 | ONCOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 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 | HHUA(RCB0658) |