Evidence map›Paper›PMID 40410129›Full record

ArticleNature communications2025

p53-inducible lncRNA LOC644656 causes genotoxic stress-induced stem cell maldifferentiation and cancer chemoresistance.

Ai Tamura, Kazuyuki Yamagata, Takashi Kono, Masanori Fujimoto, Takahiro Fuchigami, Motoi Nishimura, Masataka Yokoyama, Akitoshi Nakayama, Naoko Hashimoto, Ikki Sakuma and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Ai Tamura *Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Kazuyuki Yamagata *Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Takashi KonoDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Masanori FujimotoDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Takahiro FuchigamiDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Motoi NishimuraDivision of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, 260-8677, Chiba, Japan.
Masataka YokoyamaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Akitoshi NakayamaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Naoko HashimotoDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Ikki SakumaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Nobuyuki MitsukawaDepartment of Plastic Surgery, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Yusuke KawashimaDepartment of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Chiba, 292-0818, Japan.ORCID http://orcid.org/0000-0002-9779-8199
Osamu OharaDepartment of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Chiba, 292-0818, Japan.ORCID http://orcid.org/0000-0002-3328-9571
Shinichiro MotohashiDepartment of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Eiryo KawakamiDepartment of Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.ORCID http://orcid.org/0000-0001-9955-4342
Takashi MikiResearch Institute of Disaster Medicine, Chiba University, Chiba, 260-8670, Japan.ORCID http://orcid.org/0000-0001-5741-1626
Atsushi OnoderaResearch Institute of Disaster Medicine, Chiba University, Chiba, 260-8670, Japan.
Tomoaki TanakaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan. tomoaki@restaff.chiba-u.jp.ORCID http://orcid.org/0000-0002-9761-1750

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) JPJSCCA20200006Ministry of Education, Culture, Sports, Science and Technology (MEXT) 18K07439Ministry of Education, Culture, Sports, Science and Technology (MEXT) 18K08464Ministry of Education, Culture, Sports, Science and Technology (MEXT) 19H03708Ministry of Education, Culture, Sports, Science and Technology (MEXT) 19K07635Ministry of Education, Culture, Sports, Science and Technology (MEXT) 19K08972Ministry of Education, Culture, Sports, Science and Technology (MEXT) 20K07561Ministry of Education, Culture, Sports, Science and Technology (MEXT) 20K08397Ministry of Education, Culture, Sports, Science and Technology (MEXT) 21H02974Ministry of Education, Culture, Sports, Science and Technology (MEXT) 21K08524Ministry of Education, Culture, Sports, Science and Technology (MEXT) 21K19398Ministry of Education, Culture, Sports, Science and Technology (MEXT) 22300325Ministry of Education, Culture, Sports, Science and Technology (MEXT) 22K07205Ministry of Education, Culture, Sports, Science and Technology (MEXT) 22K08619Ministry of Education, Culture, Sports, Science and Technology (MEXT) 22K08644Ministry of Education, Culture, Sports, Science and Technology (MEXT) 23H02809Ministry of Education, Culture, Sports, Science and Technology (MEXT) 23K17429Ministry of Education, Culture, Sports, Science and Technology (MEXT) 24K10279
6 · The paper itself

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.

Indexed as

Cell DifferentiationDNA DamageDrug Resistance, NeoplasmNeoplasmsRNA, Long NoncodingTumor Suppressor Protein p53AnimalsCell Line, TumorHistone DemethylasesHuman Embryonic Stem CellsHumansMiceOctamer Transcription Factor-3Signal TransductionTransforming Growth Factor betaHistone DemethylasesOctamer Transcription Factor-3POU5F1 protein, humanRNA, Long NoncodingTP53 protein, humanTransforming Growth Factor betaTumor Suppressor Protein p53

Identifiers

PMID40410129
PMCPMC12102190

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.