Evidence map›Paper›PMID 39407269›Full record

ArticleJournal of nanobiotechnology2024

Hypoxic glioma-derived exosomal miR-25-3p promotes macrophage M2 polarization by activating the PI3K-AKT-mTOR signaling pathway.

Zhiwei Xue, Junzhi Liu, Wenchen Xing, Feiyu Mu, Yanzhao Wu, Jiangli Zhao, Xuchen Liu, Donghai Wang, Jian Wang, Xingang Li and 2 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
–field-weighted citation impact
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

53 citing papers in PubMed.

  1. ROS-responsive HBioactive materials · 2027
    Article
  2. Therapeutic potential of targeting macrophage polarization in metastatic gastric cancer: a review on core mechanisms and clinical progress.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  3. Understanding how hypoxia contributes to liver cancer stem cells maintenance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  4. Article
  5. Translational cancer research · 2026
    Article
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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.

Zhiwei Xue *Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Junzhi Liu *Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Wenchen XingDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Feiyu MuDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Yanzhao WuDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Jiangli ZhaoDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Xuchen LiuDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Donghai WangDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Jian WangDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Xingang LiDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China. lixg@sdu.edu.cn.
Jiwei WangDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China. Jiwei.wang@email.sdu.edu.cn.
Bin HuangDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China. hb@sdu.edu.cn.

Funding

National Natural Science Foundation of China 82203760Shandong Provincial Laboratory Project SYS202202, JNL-2022003AShandong Provincial Laboratory Project SYS202202, JNL-2022042CThe Clinical Research Center of Shandong University 2020SDUCRCB002The Department of Science & Technology of Shandong Province ZR2019ZD33The Special Foundation for Taishan Scholars tshw201502056
6 · The paper itself

Abstract

backgroundExosomes (EXO) play crucial roles in intercellular communication and glioma microenvironment modulation. Tumor-associated macrophages are more likely to become M2-like type macrophages in the immunosuppressive microenvironment. Here, we aimed to investigate the effects and molecular mechanisms of hypoxic glioma-derived exosomes mediated M2-like macrophage polarization.

methodsHighly expressed miRNAs in exosomes derived from glioma cells cultured under hypoxia condition compared to normoxic condition were identified through microRNA sequencing. The polarization status of macrophages was determined using qRT-PCR, Western blotting, flow cytometry, and immunohistochemistry. By using RNA-seq, we aimed to identify the downstream target genes regulated by miR-25-3p in macrophages and investigate the mechanistic pathways through which it exerts its effects. The proliferation and migration capabilities of glioma cells were assessed through EdU, Transwell assays, and in vivo experiments.

resultsWe found that miR-25-3p was upregulated in the exosomes derived from hypoxic glioma cells and can be transferred to the macrophage. In macrophages, miR-25-3p downregulates the expression of PHLPP2, thereby activating the PI3K-AKT-mTOR signaling pathway, ultimately leading to macrophage M2 polarization. As part of a feedback loop, M2-polarized macrophages can, in turn, promote malignant glioma progression.

conclusionOur study reveals that miR-25-3p from hypoxic glioma cells is delivered to macrophages via exosomes as a mediator, promoting M2 polarization of macrophages through the miR-25-3p/PHLPP2/PI3K-AKT signaling pathway. This study suggests that targeted interventions to modulate miR-25-3p expression, transmission, or inhibition of PI3K-AKT pathway activation can disrupt the immune-suppressive microenvironment, providing a novel approach for immunotherapy in gliomas.

Indexed as

ExosomesGliomaMacrophagesMicroRNAsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesAnimalsCell HypoxiaCell Line, TumorCell ProliferationHumansMaleMiceMice, NudeMicroRNAsMIRN25 microRNA, humanMTOR protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAKT-mTORExosomesGliomamiRNAsPHLPP2

Identifiers

PMID39407269
PMCPMC11481566

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.