論文 - 詳細
| RRC ID | 72538 |
|---|---|
| 著者 | Hirata Y, Murai N, Yanaihara N, Saito M, Saito M, Urashima M, Murakami Y, Matsufuji S, Okamoto A. |
| タイトル | MicroRNA-21 is a candidate driver gene for 17q23-25 amplification in ovarian clear cell carcinoma. |
| ジャーナル | BMC Cancer |
| Abstract |
BACKGROUND:Epithelial ovarian cancer (EOC) is the most common cause of gynecological malignancy-related mortality. Ovarian clear cell carcinoma (CCC) has unique clinical characteristics and behaviors that differ from other histological types of EOC, including a frequent association with endometriosis and a highly chemoresistant nature, resulting in poor prognosis. However, factors underlying its malignant behavior are still poorly understood. Aberrant expression of microRNAs has been shown to be involved in oncogenesis, and microRNA-21 (miR-21) is frequently overexpressed in many types of cancers. The aim of this study was to investigate the role of miR-21 in 17q23-25 amplification associated with CCC oncogenesis. METHODS:We identified 17q23-25 copy number aberrations among 28 primary CCC tumors by using a comparative genomic hybridization method. Next, we measured expression levels of the candidate target genes, miR-21 and PPM1D, for 17q23-25 amplification by real-time RT-PCR analysis and compared those data with copy number status and clinicopathological features. In addition, immunohistochemical analysis of PTEN (a potential target of miR-21) was performed using the same primary CCC cases. We investigated the biological significance of miR-21 overexpression in CCC using a loss-of-function antisense approach. RESULTS:17q23-25 amplification with both miR-21 overexpression and PTEN protein loss was detected in 4/28 CCC cases (14.2%). The patients with 17q23-25 amplification had significantly shorter progression-free and overall survival than those without 17q23-25 amplification (log-rank test: p = 0.0496; p = 0.0469, respectively). A significant correlation was observed between miR-21 overexpression and endometriosis. Both PTEN mRNA and PTEN protein expression were increased by miR-21 knockdown in CCC cells. We also confirmed that miR-21 directly bound to the 3'-untranslated region of PTEN mRNA using a dual-luciferase reporter assay. CONCLUSIONS:MiR-21 is a possible driver gene other than PPM1D for 17q23-25 amplification in CCC. Aberrant expression of miR-21 by chromosomal amplification might play an important role in CCC carcinogenesis through the regulation of the PTEN tumor suppressor gene. |
| 巻・号 | 14 |
| ページ | 799 |
| 公開日 | 2014-11-3 |
| DOI | 10.1186/1471-2407-14-799 |
| PII | 1471-2407-14-799 |
| PMID | 25366985 |
| PMC | PMC4289307 |
| MeSH | Adenocarcinoma, Clear Cell / genetics* Adenocarcinoma, Clear Cell / mortality Adenocarcinoma, Clear Cell / pathology Adult Aged Aged, 80 and over Chromosomes, Human, Pair 17 / genetics* Comparative Genomic Hybridization Female Follow-Up Studies Gene Amplification* Gene Dosage Gene Expression Gene Expression Regulation, Neoplastic Humans MicroRNAs / genetics* Middle Aged Neoplasm Metastasis Neoplasm Staging Ovarian Neoplasms / genetics* Ovarian Neoplasms / pathology PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism Prognosis |
| IF | 3.15 |
| リソース情報 | |
| ヒト・動物細胞 | JHOC-5(RCB1520) JHOC-9(RCB2226) |