論文 - 詳細
| RRC ID | 67733 |
|---|---|
| 著者 | Miyakuni K, Nishida J, Koinuma D, Nagae G, Aburatani H, Miyazono K, Ehata S. |
| タイトル | Genome-wide analysis of DNA methylation identifies the apoptosis-related gene UQCRH as a tumor suppressor in renal cancer. |
| ジャーナル | Mol Oncol |
| Abstract |
DNA hypermethylation is frequently observed in clear cell renal cell carcinoma (ccRCC) and correlates with poor clinical outcomes. However, the detailed function of DNA hypermethylation in ccRCC has not been fully uncovered. Here, we show the role of DNA methylation in ccRCC progression through the identification of a target(s) of DNA methyltransferases (DNMT). Our preclinical model of ccRCC using the serial orthotopic inoculation model showed the upregulation of DNMT3B in advanced ccRCC. Pretreatment of advanced ccRCC cells with 5-aza-deoxycytidine, a DNMT inhibitor, attenuated the formation of primary tumors through the induction of apoptosis. DNA methylated sites were analyzed genome-wide using methylation array in reference to RNA-sequencing data. The gene encoding ubiquinol cytochrome c reductase hinge protein (UQCRH), one of the components of mitochondrial complex III, was extracted as a methylation target in advanced ccRCC. Immunohistochemical analysis revealed that the expression of UQCRH in human ccRCC tissues was lower than normal adjacent tissues. Silencing of UQCRH attenuated the cytochrome c release in response to apoptotic stimuli and resulted in enhancement of primary tumor formation in vivo, implying the tumor-suppressive role of UQCRH. Moreover, 5-aza-deoxycytidine enhanced the therapeutic efficiency of mammalian target of rapamycin inhibitor everolimus in vivo. These findings suggested that the DNMT3B-induced methylation of UQCRH may contribute to renal cancer progression and implicated clinical significance of DNMT inhibitor as a therapeutic option for ccRCC. |
| 巻・号 | 16(3) |
| ページ | 732-749 |
| 公開日 | 2022-2-1 |
| DOI | 10.1002/1878-0261.13040 |
| PMID | 34133843 |
| PMC | PMC8807364 |
| MeSH | Apoptosis / genetics Carcinoma, Renal Cell* / metabolism Cell Line, Tumor DNA Methylation / genetics Electron Transport Complex III / genetics Electron Transport Complex III / metabolism Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Humans Kidney Neoplasms* / pathology |
| IF | 6.574 |
| 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 | Peer-review(Publons) |
| 各媒体での言及数の合計 | 6 |
| 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 | |
| 遺伝子材料 | CSII-CMV-RfA (RDB04386) pENTR4-H1 (RDB04395) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |