Evidence map›Paper›PMID 30736838›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma.

Zhenwei He, Xuelei Ruan, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Lianqi Shao, Di Wang, Shuyuan Shen and 2 more

Open access · goldAbstract read
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. Cited by 112 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
13.4field-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

112 citing papers in PubMed, 1 synthesis or guideline pooled it, 216 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Circular RNAs in Brain Physiology and Neurologic Diseases.Advances in experimental medicine and biology · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. The Role of miR-138 in Cardiovascular Diseases.BioMed research international · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

52 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 2 institutions in 1 country.

Zhenwei HeDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China.
Xuelei RuanDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China.
Xiaobai LiuDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Jian ZhengDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Yunhui LiuDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Libo LiuDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China.
Jun MaDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China.
Lianqi ShaoDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China.
Di WangDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Shuyuan ShenDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China.
Chunqing YangDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
Yixue XueDepartment of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, People's Republic of China. xueyixue888@163.com.
China Medical University · CNShenyang Center for Disease Control and Prevention · CN

Funding

Natural Science Foundation of China 81502179Natural Science Foundation of China 81573010Natural Science Foundation of China 81672511Natural Science Foundation of China 81872503
6 · The paper itself

Abstract

backgroundAngiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate in the regulation of the malignant behaviors of tumors. As a type of endogenous non-coding RNAs, circular RNAs (circRNAs) are abnormally expressed in various cancers and are involved in diverse tumorigeneses including angiogenesis.

methodsThe expression levels of FUS, circ_002136, miR-138-5p, SOX13, and SPON2 were determined using quantitative real-time PCR (qRT-PCR) and western blot. Transient cell transfection was performed using the Lipofectamine 3000 reagent. The RNA-binding protein immunoprecipitation (RNA-IP) and the RNA pull-down assays were used to detect the interaction between FUS and circ_002136. The dual-luciferase reporter assay system was performed to detect the binding sites of circ_002136 and miR-138-5p, miR-138-5p and SOX13. The chromatin immunoprecipitation (ChIP) assays were used to examine the interactions between transcription factor SOX13 and its target proteins .

resultsWe demonstrated that down-regulation of FUS or circ_002136 dramatically inhibited the viability, migration and tube formation of U87 glioma-exposed endothelial cells (GECs). MiR-138-5p was down-regulated in GECs and circ_002136 functionally targeted miR-138-5p in an RNA-induced silencing complex (RISC). Inhibition of circ_002136, combined with the restoration of miR-138-5p, robustly reduced the angiogenesis of GECs. As a target gene of miR-138-5p, SOX13 was overexpressed in GECs and was proved to be involved in circ_002136 and miR-138-5p-mediated angiogenesis in gliomas. In addition, we found that SOX13 was directly associated with and activated the SPON2 promoter, thereby up-regulating the expression of SPON2 at the transcriptional level. Knockdown of SPON2 suppressed the angiogenesis in GECs. More important, SOX13 activated the FUS promoter and increased its expression, forming a feedback loop.

conclusionOur data suggests that the feedback loop of FUS/circ_002136/miR-138-5p/SOX13 played a crucial role in the regulation of angiogenesis in glioma. This also provides a potential target and an alternative strategy for combined glioma therapy.

Indexed as

AnimalsCell Line, TumorDisease ProgressionGliomaHumansMaleMiceMice, NudeMicroRNAsNeovascularization, PathologicRNA-Binding Protein FUSSignal TransductionTransfectionFUS protein, humanMicroRNAsMIRN138 microRNA, humanRNA-Binding Protein FUSAngiogenesisFUS; circ_002136miR-138-5pSOX13SPON2

Identifiers

PMID30736838
PMCPMC6368736
OpenAlexW2922225941

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.