Evidence map›Paper›PMID 30064482›Full record

ArticleJournal of experimental & clinical cancer research : CR2018

Osteopontin alters DNA methylation through up-regulating DNMT1 and sensitizes CD133+/CD44+ cancer stem cells to 5 azacytidine in hepatocellular carcinoma.

Xiaomei Gao, Yuanyuan Sheng, Jing Yang, Chaoqun Wang, Rui Zhang, Ying Zhu, Ze Zhang, Kaili Zhang, Shican Yan, Haoting Sun and 10 more

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

Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

39 citing papers in PubMed, 93 citations in OpenAlex.

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  17. HCV Core protein represses DKK3 expression via epigenetic silencing and activates the Wnt/β-catenin signaling pathway during the progression of HCC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Article
  18. Review
  19. Epigenetic remodelling in human hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Xiaomei GaoDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Yuanyuan ShengDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Jing YangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Chaoqun WangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Rui ZhangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Ying ZhuDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Ze ZhangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Kaili ZhangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Shican YanDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Haoting SunDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Jinwang WeiDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Xuan WangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Xinxin YuDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Yu ZhangDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Qin LuoDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Yan ZhengDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Peng QiaoDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Yue ZhaoDepartment of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
Qiongzhu DongDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. qiongzhudong@163.com.
Lunxiu QinDepartment of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. qinlx@fudan.edu.cn.
Huashan Hospital · CNFudan University · CNUniversity Hospital Cologne · DE

Funding

China National Key Projects for Infectious Disease 2012ZX10002-012China National Natural Science Foundation 81372647National Natural Science Foundation of China (CN) 81672820the National Key Basic Research Program of China 2013CB910500the National Key Research and Development Program of China 2017YFC1308604
6 · The paper itself

Abstract

backgroundIn hepatocellular carcinoma (HCC), CD133+/CD44+ cells are one subgroup with high stemness and responsible for metastatic relapse and resistance to treatment. Our previous studies have demonstrated that osteopontin (OPN) plays critical roles in HCC metastasis. We further investigated the molecular mechanism underlying the role of OPN in regulating the stemness of HCC epigenetically and explored possible targeting strategy.

methodsCD133+/CD44+ subgroup sorting from HCC cell lines and HCC tissues was used to investigate the effects of OPN knockdown on stemness. iTRAQ and MedIP-sequencing were applied to detect the protein profile and epigenetic modification of CD133+/CD44+ subgroup with or without OPN knockdown. The antitumor effects of 5 Azacytidine were examined in cultured HCC cells and patient derived xenograft (PDX) models.

resultsOPN was accumulated in CD133+/CD44+ subgroup of HCC cells. Knocking down OPN significantly inhibited the sphere formation and stemness-related genes expression, and delayed tumor initiation of CD133+/CD44+ subgroup of HCC cells. Employing MedIP-sequencing, dot blot and iTRAQ analyses of CD133+/CD44+ SCR and CD133+/CD44+ shOPN cells, we found that OPN knockdown leaded to reduction in DNA methylation with particular enrichment in CGI. Meanwhile, DNA (cytosine-5)-methyltransferase 1 (DNMT1), the main methylation maintainer, was downregulated via proteomics analysis, which mediated OPN altering DNA methylation. Furthermore, DNMT1 upregulation could partially rescue the properties of CD133+/CD44+ shOPN cells. Both in vitro and in vivo assays showed that CD133+/CD44+ cells with high OPN levels were more sensitive to DNA methylation inhibitor, 5 Azacytidine (5 Aza). The above findings were validated in HCC primary cells, a more clinically relevant model.

conclusionsOPN induces methylome reprogramming to enhance the stemness of CD133+/CD44+ subgroup and provides the therapeutic benefits to DNMT1 targeting treatment in HCC.

Indexed as

DNA MethylationAC133 AntigenAnimalsAntimetabolites, AntineoplasticAzacitidineCarcinoma, HepatocellularCell Line, TumorDNA (Cytosine-5-)-Methyltransferase 1Gene Knockdown TechniquesHumansHyaluronan ReceptorsLiver NeoplasmsMiceMice, Inbred NODNeoplastic Stem CellsOsteopontinAC133 AntigenAntimetabolites, AntineoplasticAzacitidineCD44 protein, humanDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanHyaluronan ReceptorsOsteopontinPROM1 protein, humanSPP1 protein, humanCancer therapyCD133+/CD44+ cellsDNA methylationHepatocellular carcinomaOsteopontin

Identifiers

PMID30064482
PMCPMC6069805
OpenAlexW2885454874

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.