論文 - 詳細
| RRC ID | 84973 |
|---|---|
| 著者 | Tamura A, Yamagata K, Kono T, Fujimoto M, Fuchigami T, Nishimura M, Yokoyama M, Nakayama A, Hashimoto N, Sakuma I, Mitsukawa N, Kawashima Y, Ohara O, Motohashi S, Kawakami E, Miki T, Onodera A, Tanaka T. |
| タイトル | p53-inducible lncRNA LOC644656 causes genotoxic stress-induced stem cell maldifferentiation and cancer chemoresistance. |
| ジャーナル | Nat Commun |
| Abstract |
Genotoxic stress-induced stem cell maldifferentiation (GSMD) integrates DNA damage responses with loss of stemness and lineage-specific differentiation to prevent damaged stem cell propagation. However, molecular mechanisms governing GSMD remain unclear. Here, we identify the p53-induced long non-coding RNA LOC644656 as a key regulator of GSMD in human embryonic stem cells. LOC644656 accumulates in the nucleus upon DNA damage, disrupting pluripotency by interacting directly with POU5F1 and KDM1A/LSD1-NuRD complexes, repressing stemness genes, and activating TGF-β signaling. Additionally, LOC644656 mitigates DNA damage by binding DNA-PKcs and modulating the DNA damage response. In cancer, elevated LOC644656 correlates with poor patient survival and enhanced chemoresistance. Our findings demonstrate that LOC644656 mediates stemness suppression and resistance to genotoxic stress by coordinating DNA damage signaling and differentiation pathways. Thus, LOC644656 represents a potential therapeutic target for overcoming chemoresistance and advancing stem cell biology. |
| 巻・号 | 16(1) |
| ページ | 4818 |
| 公開日 | 2025-5-23 |
| DOI | 10.1038/s41467-025-59886-w |
| PII | 10.1038/s41467-025-59886-w |
| PMID | 40410129 |
| PMC | PMC12102190 |
| MeSH | Animals Cell Differentiation* / genetics Cell Line, Tumor DNA Damage* / genetics Drug Resistance, Neoplasm* / genetics Histone Demethylases / metabolism Human Embryonic Stem Cells / cytology Human Embryonic Stem Cells / metabolism Humans Mice Neoplasms* / drug therapy Neoplasms* / genetics Neoplasms* / pathology Octamer Transcription Factor-3 / genetics Octamer Transcription Factor-3 / metabolism RNA, Long Noncoding* / genetics RNA, Long Noncoding* / metabolism Signal Transduction Transforming Growth Factor beta / metabolism Tumor Suppressor Protein p53* / genetics Tumor Suppressor Protein p53* / metabolism |
| IF | 12.121 |
| 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 | News |
| 各媒体での言及数の合計 | 8 |
| 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 | KhES-3(HES0003) KhES-1(HES0001) |