Evidence map›Paper›PMID 41565615›Full record

ArticleNature communications2026

SNORA49 negatively regulates self-renewal of liver cancer stem cells and hepatocarcinogenesis via suppressing SOX9 transcription.

Zhibin Yi, Ziheng Zhou, Yang Gu, Yuwei Xu, Ziqi Xiao, Zhen Xiong, Jianyi Wang, Hui Guo, Ying Du, Yun Chen and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Zhibin Yi *State Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Ziheng Zhou *State Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yang Gu *State Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yuwei Xu *State Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Ziqi Xiao *State Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Zhen XiongState Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Jianyi WangState Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Hui GuoState Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Ying DuState Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yun ChenThe Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China. chenyun@njmu.edu.cn.ORCID http://orcid.org/0000-0002-4118-362X
Zusen FanState Key Laboratory of RNA Science and Engineering, State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. fanz@moon.ibp.ac.cn.ORCID http://orcid.org/0000-0002-7866-8217

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer stem cells (CSCs) play a critical role in tumor initiation, progression, and recurrence. How liver CSCs initiate their self-renewal remains elusive. Here we identify a conserved small nucleolar RNA (snoRNA), SNORA49, which is lowly expressed in liver CSCs, as a negative regulator of CSC self-renewal. SNORA49 knockout enhances the self-renewal capacity of liver CSCs and accelerates hepatocellular carcinoma (HCC) tumorigenesis, whereas overexpression of SNORA49 suppresses tumor formation. Mechanistically, in non-CSCs, SNORA49 is specifically localized in the nucleoplasm to associate with HNRNPU, blocking its interaction with ZC3H18, resulting in inhibition of SOX9 transcription. In liver CSCs, lowly expressed SNORA49 releases HNRNPU to engage with ZC3H18 and enrich on the promoter of SOX9, leading to its transcription. Of note, lipid nanoparticle (LNP)-mediated delivery of SNORA49 RNAs and antisense oligonucleotides (ASOs) targeting SOX9 exerts potent synergistic anti-tumor effect on HCC tumors. Our findings define SNORA49 as a tumor suppressor in liver CSCs, and restoring SNORA49 levels and silencing SOX9 with LNP-delivered system may provide therapeutic strategy for clinical intervention to HCC patients.

Indexed as

CarcinogenesisCarcinoma, HepatocellularLiver NeoplasmsNeoplastic Stem CellsRNA, Small NucleolarSOX9 Transcription FactorAnimalsCell Line, TumorCell Self RenewalGene Expression Regulation, NeoplasticHumansMiceTranscription, GeneticRNA, Small NucleolarSOX9 protein, humanSOX9 Transcription Factor

Identifiers

PMID41565615
PMCPMC12824223

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.