Reference - Detail
| RRC ID | 84973 |
|---|---|
| Author | 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. |
| Title | p53-inducible lncRNA LOC644656 causes genotoxic stress-induced stem cell maldifferentiation and cancer chemoresistance. |
| Journal | 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. |
| Volume | 16(1) |
| Pages | 4818 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | KhES-3(HES0003) KhES-1(HES0001) |