Evidence map›Paper›PMID 33664298›Full record

ArticleScientific reports2021

Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth.

Sahar Shekoohi, Santhanasabapathy Rajasekaran, Dhaval Patel, Shu Yang, Wang Liu, Shile Huang, Xiuping Yu, Stephan N Witt

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Review
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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 1 institution in 1 country.

Sahar ShekoohiDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Santhanasabapathy RajasekaranDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Dhaval PatelDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Shu YangDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Wang LiuDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Shile HuangDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Xiuping YuDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Stephan N WittDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. switt1@lsuhsc.edu.
Louisiana State University Health Sciences Center Shreveport · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The protein alpha-synuclein (α-syn) is unusual because, depending on its conformation and the type of cell in which it is expressed, it is pro-death or pro-survival, triggering neurodegeneration in Parkinson's disease and enhancing cell survival of some melanomas. To probe the function of α-syn in melanoma, we used CRISPR/Cas9 to knockout SNCA, the gene that codes for α-syn, in SK-Mel-28 melanoma cells. The SNCA-knockout clones in culture exhibited a decrease in the transferrin receptor 1 (TfR1), an increase in ferritin, an increase of reactive oxygen species and proliferated slower than control cells. These SNCA-knockout clones grafted into SCID mice grew significantly slower than the SK-Mel-28 control cells that expressed α-syn. In the excised SNCA-knockout xenografts, TfR1 decreased 3.3-fold, ferritin increased 6.2-fold, the divalent metal ion transporter 1 (DMT1) increased threefold, and the iron exporter ferroportin (FPN1) decreased twofold relative to control xenografts. The excised SNCA-KO tumors exhibited significantly more ferric iron and TUNEL staining relative to the control melanoma xenografts. Collectively, depletion of α-syn in SK-Mel-28 cells dysregulates cellular iron metabolism, especially in xenografts, yielding melanoma cells that are deficient in TfR1 and FPN1, that accumulate ferric iron and ferritin, and that undergo apoptosis relative to control cells expressing α-syn.

Indexed as

alpha-SynucleinAnimalsAntigens, CDCation Transport ProteinsCell ProliferationCell SurvivalCRISPR-Cas SystemsFerritinsFerroportinGene Expression Regulation, NeoplasticGene Knockout TechniquesHeterograftsHumansIronMelanomaMicealpha-SynucleinAntigens, CDCation Transport ProteinsCD71 antigenFerritinsFerroportinIronReceptors, TransferrinSNCA protein, human

Identifiers

PMID33664298
PMCPMC7933179
OpenAlexW3133735843

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.