Evidence map›Paper›PMID 32894165›Full record

ArticleJournal of experimental & clinical cancer research : CR2020

The U2AF2 /circRNA ARF1/miR-342-3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells.

Yang Jiang, Jinpeng Zhou, Junshuang Zhao, Haiying Zhang, Long Li, Hao Li, Lian Chen, Jiangfeng Hu, Wei Zheng, Zhitao Jing

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

Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
8.5field-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

69 citing papers in PubMed, 128 citations in OpenAlex.

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9 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

10 authors at 4 institutions in 1 country.

Yang JiangDepartment of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China.
Jinpeng ZhouDepartment of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China.
Junshuang ZhaoDepartment of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China.
Haiying ZhangInternational Education College, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan East Road, Shenyang, 110042, China.
Long LiDepartment of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China.
Hao LiDepartment of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China.
Lian ChenDepartment of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China.
Jiangfeng HuDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100 Haining Road, Shanghai, 20080, China.
Wei ZhengDepartment of Histology and Embryology, College of Basic Medical Science, China Medical University, No. 77 Puhe Road, Shenyang, 110122, China.
Zhitao JingDepartment of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China. jingzhitao@hotmail.com.
China Medical University · CNFirst Hospital of China Medical University · CNLiaoning University of Traditional Chinese Medicine · CNShanghai First People's Hospital · CN

Funding

Horizontal issues of Jiangsu Xiansheng JSXSZD-SA2020-06-004Liaoning BaiQianWan Talents Program 2019-B45National Natural Science Foundation of China 81101917National Natural Science Foundation of China 81900544Natural Science Foundation of Liaoning Province 20170541022Shanghai Sailing Program 19YF1439000the Social Development Program from Shenyang Science and Technology Bureau, China 20-205-4-075
6 · The paper itself

Abstract

backgroundGlioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma.

methodsBioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342-3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules.

resultsWe first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342-3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival.

conclusionsOur study identified a novel feedback loop among U2AF2, cARF1, miR-342-3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

Indexed as

ADP-Ribosylation Factor 1AnimalsApoptosisBiomarkers, TumorBrain NeoplasmsCell ProliferationFeedback, PhysiologicalFemaleGene Expression Regulation, NeoplasticGliomaHumansLIM-Homeodomain ProteinsMaleMiceMice, Inbred BALB CMice, NudeADP-Ribosylation Factor 1ARF1 protein, humanBiomarkers, TumorISL2 protein, humanLIM-Homeodomain ProteinsMicroRNAsMIRN342 microRNA, humanNerve Tissue ProteinsRNA, CircularSplicing Factor U2AFTranscription FactorsU2AF2 protein, humanAngiogenesiscircRNA ARF1Glioma stem cellsISL2miR-342–3pU2AF2

Identifiers

PMID32894165
PMCPMC7487667
OpenAlexW3083237971

What OpenQuestion holds

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LicenceCC BY
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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.