Evidence map›Paper›PMID 34799992›Full record

ArticleCancer medicine2022

Dcf1 induces glioblastoma cells apoptosis by blocking autophagy.

Guanghong Luo, Ruili Feng, Wengang Li, Yanlu Chen, Yangyang Sun, Junfeng Ma, Yanhong Duo, Tieqiao Wen

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

Article in Cancer medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Guanghong LuoLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.ORCID 0000-0002-3710-7077
Ruili FengLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.
Wengang LiDepartment of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Yanlu ChenLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.
Yangyang SunLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.
Junfeng MaDepartment of Neurosurgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Yanhong DuoDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Tieqiao WenLaboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.
Shanghai University · CNFudan University · CNKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDcf1 has been demonstrated to play vital roles in many CNS diseases, it also has a destructive role on cell mitochondria in glioma cells and promotes the autophagy. Hitherto, it is unclear whether the viability of glioblastoma cells is affected by Dcf1, in particular Dcf1 possesses broad localization on different organelles, and the organelles interaction frequently implicated in cancer cells survival.

methodsSurgically excised WHO grade IV human glioblastoma tissues were collected and cells isolated for culturing. RT-PCR and DNA sequencing assay to estimate the abundance and mutation of Dcf1. iTRAQ sequencing and bioinformatic analysis were performed. Subsequently, immunoprecipitation assay to evaluate the degradation of HistoneH2A isomers by UBA52 ubiquitylation. Transmission electron microscopy (TEM) was applied to observe the structure change of mitochondria and autophagosome. Organelle isolated assay to determine the distribution of protein. Cell cycle and apoptosis were evaluated by flow cytometric assays.

resultsDcf1 was downregulated in WHO grade IV tumor without mutation, and overexpression of Dcf1 was found to significantly regulate glioblastoma cells. One hundred and seventy-six differentially expressed proteins were identified by iTRAQ sequencing. Furthermore, we confirmed that overexpression of Dcf1 destabilized the structure of the nucleosome via UBA52 ubiquitination to downregulate HistoneH2A.X but not macroH2A or HistoneH2A.Z, decreased the mitochondrial DNA copy number and inhibited the mitochondrial biogenesis, thus causing mitochondrial destruction and dysfunction in order to supply cellular energy and induce mitophagy preferentially but not apoptosis. Dcf1 also has disrupted the integrity of lysosomes to block autolysosome degradation and autophagy and to increase the release of Cathepsin B and D from lysosomes into cytosol. These proteins cleaved and activated BID to induce glioblastoma cells apoptosis.

conclusionsIn this study, we demonstrated that unmutated Dcf1 expression is negatively related to the malignancy of glioblastoma, Dcf1 overexpression causes nucleosomes destabilization, mitochondria destruction and dysfunction to induce mitophagy preferentially, and block autophagy by impairing lysosomes to induce apoptosis in glioblastoma.

Indexed as

ApoptosisAutophagyCell Line, TumorGene Expression Regulation, NeoplasticGlioblastomaHistonesHumansLysosomesMembrane ProteinsMitochondriaMitophagyNerve Tissue ProteinsNucleosomesOrganelle BiogenesisHistonesMembrane ProteinsNerve Tissue ProteinsNucleosomesTMEM59 protein, humanapoptosisDcf1glioblastomalysosomemitochondriamitophagy

Identifiers

PMID34799992
PMCPMC8704163
OpenAlexW3214486683

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.