Evidence map›Paper›PMID 42457924›Full record

ArticleCell death and differentiation2026

Targeting POLRMT-driven epigenetic remodeling of Wnt/β-catenin to eradicate colorectal cancer stem cell proliferation.

Lei Tang, Siheng Nie, Jialong Qi, Rui Yu, Jinglan Zhang, Ran Zhu, Qi Li, Xiaoshuang Zhou, Shaoxing Dai, Li Wang and 3 more

Abstract read
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In one paragraph

Article in Cell death and differentiation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Lei Tang *Medical School, Kunming University of Science and Technology, Kunming, PR China.
Siheng Nie *Medical School, Kunming University of Science and Technology, Kunming, PR China.
Jialong Qi *Yunnan Province Clinical Medical Center for Digestive System Diseases, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, PR China.
Rui YuMedical School, Kunming University of Science and Technology, Kunming, PR China.
Jinglan ZhangMedical School, Kunming University of Science and Technology, Kunming, PR China.
Ran ZhuState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, PR China.ORCID http://orcid.org/0000-0003-0874-9369
Qi LiMedical School, Kunming University of Science and Technology, Kunming, PR China.
Xiaoshuang ZhouMedical School, Kunming University of Science and Technology, Kunming, PR China.
Shaoxing DaiState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, PR China.ORCID http://orcid.org/0000-0002-6919-2034
Li WangDepartment of Pathology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, PR China.
Maorong ChenYunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, PR China.
Fan YangMedical School, Kunming University of Science and Technology, Kunming, PR China.
Jihong ZhangMedical School, Kunming University of Science and Technology, Kunming, PR China. zhjihong2000@kust.edu.cn.ORCID http://orcid.org/0000-0001-7523-8265

Funding

Yunnan Provincial Department of Education (Department of Education, Yunnan Province) 2025Y0283
6 · The paper itself

Abstract

Colorectal cancer stem cells (CSCs) drive tumor progression through poorly understood metabolic-epigenetic crosstalk. Here, we identify mitochondrial RNA polymerase POLRMT as a key link connecting mitochondrial transcription to CSC maintenance. Clinically, POLRMT is overexpressed in colorectal cancer (CRC) tissues and correlates with poor prognosis. Genetic ablation or pharmacological inhibition of POLRMT suppresses CSC self-renewal and tumorigenicity across cell line-derived CSCs, CRC organoids, and xenograft models. Mechanistically, POLRMT deficiency triggers mitochondrial dysfunction, which unexpectedly elevates the demethylase KDM6B expression, α-ketoglutarate (α-KG) levels, and Dickkopf-1 (DKK1) expression, thereby transcriptionally silencing Wnt/β-catenin signaling and collapsing the CSC niche. Restoration of β-catenin rescues tumorigenicity in POLRMT-knockout (KO) cells, confirming the hierarchy of this signaling cascade. Crucially, POLRMT catalytic activity and mitochondrial localization are indispensable for sustaining this axis. Our work unveils POLRMT as a metabolic gatekeeper that licenses CSC plasticity through KDM6B-α-KG/H3K27me3-mediated chromatin remodeling, proposing the mitochondrial transcription machinery as a therapeutic target for dismantling the CSC hierarchy in CRC.

Identifiers

PMID42457924

What OpenQuestion holds

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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.