Evidence map›Paper›PMID 33707417›Full record

ArticleCell death & disease2021

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis.

Gao Liu, Jian Sun, Zhang-Fu Yang, Cheng Zhou, Pei-Yun Zhou, Ruo-Yu Guan, Bao-Ye Sun, Zhu-Tao Wang, Jian Zhou, Jia Fan and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 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
6.9field-weighted citation impact, top 2% 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, 117 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026
    Review
  6. Role of non-coding RNAs in OOncology letters · 2026
    Review
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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

12 authors at 1 institution in 1 country.

Gao LiuDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.ORCID http://orcid.org/0000-0003-2861-2431
Jian SunDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Zhang-Fu YangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Cheng ZhouDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Pei-Yun ZhouDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Ruo-Yu GuanDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Bao-Ye SunDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Zhu-Tao WangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Jian ZhouDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Jia FanDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.ORCID http://orcid.org/0000-0001-5158-629X
Shuang-Jian QiuDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China. qiu.shuangjian@zs-hospital.sh.cn.
Yong YiDepartment of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China. yi.yong@zs-hospital.sh.cn.
Sun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are commonly acquired activated extracellular matrix (ECM)-producing myofibroblasts, a phenotypes with multiple roles in hepatic fibrogenesis and carcinogenesis via crosstalk with cohabitating stromal/cancer cells. Here, we discovered a mechanism whereby CAF-derived cytokines enhance hepatocellular carcinoma (HCC) progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells. CAFs secreted significantly higher levels of CXCL11 than normal fibroblasts (NFs), and CXCL11 also had comparatively higher expressions in HCC tissues, particularly in metastatic tissues, than para-carcinoma tissues. Both CAF-derived and experimentally introduced CXCL11 promoted HCC cell migration. Likewise, CAFs promoted tumor migration in orthotopic models, as shown by an increased number of tumor nodules, whereas CXCL11 silencing triggered a decrease of it. CXCL11 stimulation upregulated circUBAP2 expression, which was significantly higher in HCC tissues than para-carcinoma tissues. Silencing circUBAP2 reversed the effects of CXCL11 on the expression of IL-1β/IL-17 and HCC cell migration. Further downstream, the IFIT1 and IFIT3 levels were significantly upregulated in HCC cells upon CXCL11 stimulation, but downregulated upon circUBAP2 silencing. IFIT1 or IFIT3 silencing reduced the expression of IL-17 and IL-1β, and attenuated the migration capability of HCC cells. Herein, circUBAP2 counteracted miR-4756-mediated inhibition on IFIT1/3 via sponging miR-4756. miR-4756 inhibition reversed the effects induced by circUBAP2 silencing on the IL-17 and IL-1β levels and HCC cell migration. In orthotopic models, miR-4756 inhibition also reversed the effects on metastatic progression induced by silencing circUBAP2.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCancer-Associated FibroblastsCarcinoma, HepatocellularCell Line, TumorCell MovementChemokine CXCL11Gene Expression Regulation, NeoplasticHumansInterleukin-17Interleukin-1betaIntracellular Signaling Peptides and ProteinsLiver NeoplasmsLung NeoplasmsMaleMiceAdaptor Proteins, Signal TransducingChemokine CXCL11CXCL11 protein, humanIFIT1 protein, humanIFIT3 protein, humanIL1B protein, humanInterleukin-17Interleukin-1betaIntracellular Signaling Peptides and ProteinsMicroRNAsMIRN4756 microRNA, humanRNA-Binding ProteinsRNA, Circular

Identifiers

PMID33707417
PMCPMC7952559
OpenAlexW3135497466

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.