Evidence map›Paper›PMID 34285192›Full record

ArticleCell death & disease2021

TGF-β1-mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p/EPB41L5 axis to promote non-small cell lung cancer brain metastasis.

Dongming Wu, Shihua Deng, Li Li, Teng Liu, Ting Zhang, Jing Li, Ye Yu, Ying Xu

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

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% 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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Dongming Wu *School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Shihua Deng *School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Li LiSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Teng LiuSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Ting ZhangSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Jing LiSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Ye YuSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China.
Ying XuSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, PR China. yingxu825@126.com.
Chengdu Medical College · CNFirst Affiliated Hospital of Chengdu Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brain metastases remain a major problem in patients with advanced non-small cell lung cancer (NSCLC). The permeability of the blood-brain barrier (BBB) is highly increased during lung cancer brain metastasis; however, the underlying mechanism remains largely unknown. We previously found that lnc-MMP2-2 is highly enriched in tumor growth factor (TGF)-β1-mediated exosomes and regulates the migration of lung cancer cells. This study aimed to explore the role of exosomal lnc-MMP2-2 in the regulation of BBB and NSCLC brain metastasis. Here, using endothelial monolayers and mouse models, we found that TGF-β1-mediated NSCLC-derived exosomes efficiently destroyed tight junctions and the integrity of these natural barriers. Overexpression of lnc-MMP2-2 in human brain microvascular endothelial cells increased vascular permeability in endothelial monolayers, whereas inhibition of lnc-MMP2-2 alleviated these effects. Furthermore, lnc-MMP2-2 knockdown markedly reduced NSCLC brain metastasis in vivo. Mechanistically, through luciferase reporter assays, RNA pull-down assay, and Ago2 RNA immunoprecipitation assay, we showed that lnc-MMP2-2 served as a microRNA sponge or a competing endogenous RNA for miR-1207-5p and consequently modulated the derepression of EPB41L5. In conclusion, TGF-β1-mediated exosomal lnc-MMP2-2 increases BBB permeability to promote NSCLC brain metastasis. Thus, exosomal lnc-MMP2-2 may be a potential biomarker and therapeutic target against lung cancer brain metastasis.

Indexed as

AnimalsBase SequenceBinding SitesBlood-Brain BarrierBrain NeoplasmsCarcinoma, Non-Small-Cell LungCell Line, TumorDown-RegulationEndothelial CellsEndotheliumExosomesFemaleHumansLung NeoplasmsMembrane ProteinsMesodermEPB41L5 protein, humanMembrane ProteinsMicroRNAsMIRN1207 microRNA, humanRNA, Long NoncodingTight Junction ProteinsTransforming Growth Factor beta1

Identifiers

PMID34285192
PMCPMC8292445
OpenAlexW3186849348

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.