Evidence map›Paper›PMID 31097000›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

MiR-29b/Sp1/FUT4 axis modulates the malignancy of leukemia stem cells by regulating fucosylation via Wnt/β-catenin pathway in acute myeloid leukemia.

Bing Liu, Hongye Ma, Qianqian Liu, Yang Xiao, Shimeng Pan, Huimin Zhou, Li Jia

RetractedErratum issuedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 51 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Bing LiuCollege of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China.
Hongye MaDepartment of Clinical Laboratory, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital University of Medicine Sciences, Beijing, 100010, China.
Qianqian LiuCollege of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China.
Yang XiaoCollege of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China.
Shimeng PanCollege of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China.
Huimin ZhouDepartment of Microbiology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
Li JiaCollege of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China. jiali0386@sina.com.ORCID http://orcid.org/0000-0003-3152-3253
Dalian Medical University · CNBeijing Hospital of Traditional Chinese Medicine · CN

Funding

National Natural Science Foundation of China 81772277
6 · The paper itself

Abstract

backgroundAcute myeloid leukemia (AML) is initiated and maintained by a unique, small subset of leukemia stem cells (LSCs). LSCs are characterized by unrestricted self-renewal and contribute to the malignancy of leukemia. Aberrant protein fucosylation is associated with AML progression. However, it is still less understood that the miR-29b/Sp1/FUT4 crosstalk involved in the fucosylation-mediated LSCs malignancy in AML.

methodsAML cell lines were sorted by magnetic microbeads to obtain the CD34 + CD38- sub-population. The key biomarkers for LSCs were identified by flow cytometry. Fucosyltransferase genes were screened by qRT-PCR, and FUT4 was focused. Effect of FUT4 on LSCs malignancy was determined by CCK8 assay, sphere formation assay, immunofluorescence staining, apoptosis and in vivo xenografts experiments. The linkage of FUT4 promoter and Sp1 was confirmed by dual-luciferase reporter gene assay. ChIP-PCR assay was used to show the directly binding of Sp1 and FUT4 promoter. Activity of Wnt//β-catenin pathway was determined by western blot. Overall survival curves were diagrammed by Kaplan-Meier analysis.

resultsHere, the expressional profiles of 11 fucosyltransferase genes were different comparing LSCs and non-LSCs of KG-1a and MOLM13 cells, whereas CD34 + CD38- cells exhibited higher expression of FUT4. Functionally, alteration of FUT4 in CD34 + CD38- cells modulated LSCs malignant behaviors both in vitro and in vivo. Transcriptional inhibitor actinomycin D (Act D) or translational inhibitor cycloheximide (CHX) prevented LSCs progression, and Sp1 was identified as the efficient regulator of FUT4 transcription. Moreover, miR-29b directly affected the binding of Sp1 and FUT4 promoter region, which further mediated LSCs proliferation, apoptosis and drug-resistance through fucosylated-CD44 via activation of Wnt/β-catenin pathway. Clinically, Sp1 and FUT4 were up-regulated and positively correlated with poor overall survival of AML patients.

conclusionThese data indicated that miR-29b/Sp1/FUT4 axis promoted the malignant behaviors of LSCs by regulating fucosylated CD44 via Wnt/β-catenin pathway. Identifying LSCs surface markers and targeting LSCs were important for the development of potential therapies in AML.

Indexed as

Wnt Signaling PathwayAnimalsBiomarkers, TumorCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleFucosyltransferasesGene Expression ProfilingGene Expression Regulation, LeukemicHumansKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleMiceMicroRNAsBiomarkers, TumorFucosyltransferasesFUT4 protein, humanMicroRNAsMIRN29a microRNA, humanSP1 protein, humanSp1 Transcription FactorAMLFUT4LSCsmiR-29bSp1Wnt/β-catenin pathway

Identifiers

PMID31097000
PMCPMC6524323
OpenAlexW2947738124

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.