Evidence map›Paper›PMID 38750472›Full record

ArticleCell communication and signaling : CCS2024

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways.

Yunji Yan, Shengwei Bai, Hongxi Han, Junqiang Dai, Liang Niu, Hongyu Wang, Qiang Dong, Hang Yin, Guoqiang Yuan, Yawen Pan

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

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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

10 authors.

Yunji Yan *Department of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Shengwei Bai *Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.
Hongxi HanDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Junqiang DaiDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Liang NiuDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Hongyu WangDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Qiang DongDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Hang YinDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
Guoqiang YuanDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China. yuangq08@lzu.edu.cn.
Yawen PanDepartment of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China. pyw@lzu.edu.cn.ORCID 0000-0003-0533-7844

Funding

Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital CY2022-QN-A12Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital CY2022-QN-B05Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital CY2022-YB-A05National Natural Science Foundation of China 81960541National Natural Science Foundation of China 82060455Natural Science Foundation of Gansu Province 21JR7RA426Natural Science Foundation of Gansu Province 22JR11RA079Natural Science Foundation of Gansu Province 23JRRA1645
6 · The paper itself

Abstract

backgroundIn the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive.

methodsLentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model.

resultsTrem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β, and caused further DNA damage and promoted the apoptosis rate of tumor cells.

conclusionsOur findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

Indexed as

GliomaMembrane GlycoproteinsMicrogliaReceptors, ImmunologicSignal TransductionAnimalsApoptosisCell Line, TumorCell MovementCell ProliferationDisease ProgressionGene Knockdown TechniquesHumansInflammationJanus Kinase 2MiceJanus Kinase 2Membrane GlycoproteinsNF-kappa BReceptors, ImmunologicSTAT3 Transcription FactorTREM2 protein, humanTrem2 protein, mouseGlioblastomaGliomaMicrogliaMicroglial polarizationStat1 proteinTrem2 protein

Identifiers

PMID38750472
PMCPMC11094905

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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.