Evidence map›Paper›PMID 34649567›Full record

ArticleMolecular cancer2021

Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling.

Yang Gu, Yanying Wang, Luyun He, Jiahang Zhang, Xiaoxiao Zhu, Nian Liu, Jianyi Wang, Tiankun Lu, Lei He, Yong Tian and 1 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% of its field
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

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.

  1. A novel regulator in cancer initiation and progression: long noncoding RNA SHNG9.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Circular RNAs: key regulators in cancer stem cell dynamics.Molecular genetics and genomics : MGG · 2026
    Review
  8. Review
  9. Article
  10. The Roles of ProteinCancer communications (London, England) · 2026
    Review
  11. Article
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  18. Science advances · 2025
    Article
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  20. Article

29 more citing papers are in PubMed but not listed here.

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 at 4 institutions in 1 country.

Yang Gu *CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Yanying Wang *CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. wangyanying@moon.ibp.ac.cn.
Luyun He *CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Jiahang Zhang *CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Xiaoxiao Zhu *CAS Key Laboratory of RNA Biology; Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Nian LiuCAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Jianyi WangCAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Tiankun LuCAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Lei HeDepartment of Hepatobiliary Surgery, PLA General Hospital, Beijing, 100853, China.
Yong TianUniversity of Chinese Academy of Sciences, Beijing, 100049, China. ytian@ibp.ac.cn.
Zusen FanCAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. fanz@moon.ibp.ac.cn.
University of Chinese Academy of Sciences · CNChinese Academy of Sciences · CNInstitute of Biophysics · CNZhengzhou University · CN

Funding

National Key R&D Program of China 2020YFA0803501, 2019YFA0508501national natural science foundation of china 82130088, 81921003, 82022058, 92042302, 31930036, 91940305, 81872413, 81772646, 32070533
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive.

methodsCircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology.

resultsCircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development.

conclusionOur findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.

Indexed as

RNA, CircularAnimalsbeta KaryopherinsBiomarkers, TumorCarcinoma, HepatocellularCell Line, TumorCell Self RenewalDisease Models, AnimalDisease SusceptibilityGene DosageGene Expression Regulation, NeoplasticHedgehog ProteinsHumansImmunohistochemistryLiver NeoplasmsMicebeta KaryopherinsBiomarkers, TumorHedgehog ProteinsIPO11 protein, humanRNA, Circularcancer initiating cellcircIPO11Hedgehog signalingLiver cancerSelf-renewal

Identifiers

PMID34649567
PMCPMC8515748
OpenAlexW3206219396

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.