Evidence map›Paper›PMID 30734978›Full record

ArticleChembiochem : a European journal of chemical biology2019

Genome-Scale CRISPR/Cas9 Screening Reveals Squalene Epoxidase as a Susceptibility Factor for Cytotoxicity of Malformin A1.

Yukio Koizumi, Jun Fukushima, Yayoi Kobayashi, Ayumi Kadowaki, Miyuki Natsui, Tomokazu Yamaguchi, Yumiko Imai, Toshihiro Sugiyama, Keiji Kuba

Open access · hybridAbstract read
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 55% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

9 authors at 3 institutions in 1 country.

Yukio KoizumiDepartment of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.ORCID 0000-0002-5509-8098
Jun FukushimaDepartment of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, 241-438 Kaidobata-Nishi, Shimoshinjo-Nakano, Akita, 010-0195, Japan.
Yayoi KobayashiDepartment of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, 241-438 Kaidobata-Nishi, Shimoshinjo-Nakano, Akita, 010-0195, Japan.
Ayumi KadowakiDepartment of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Miyuki NatsuiDepartment of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Tomokazu YamaguchiDepartment of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Yumiko ImaiLaboratory of Regulation of Intractable Infectious Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Toshihiro SugiyamaDepartment of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Keiji KubaDepartment of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.ORCID 0000-0002-2203-5293
Akita University · JPAkita Prefectural University · JPNational Institute of Biomedical Innovation, Health and Nutrition · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malformin A1 (MA1) is a fungus-produced cyclic pentapeptide. MA1 exhibits teratogenicity to plants, fibrinolysis-enhancing activity, and cytotoxicity to mammalian cells. To clarify the cytotoxic mechanism of MA1, we screened for the genes involved in the cytotoxicity of MA1 in monocytoid U937 cells by using a CRISPR/Cas9-based genome-wide knockout library. Screening was performed by positive selection for cells that were resistant to MA1 treatment, and single guide RNAs (sgRNAs) integrated into MA1-resistant cells were analyzed by high-throughput sequencing. As a result of the evaluation of sgRNAs that were enriched in MA1-resistant cells, SQLE, which encodes squalene epoxidase, was identified as a candidate gene. SQLE-depleted U937 cells were viable in the presence of MA1, and squalene epoxidase inhibitor conferred MA1 resistance to wild-type cells. These results indicate that squalene epoxidase is implicated in the cytotoxicity of MA1. This finding represents a new insight into applications of MA1 for treating ischemic diseases.

Indexed as

Aspergillus nigerCell SurvivalCRISPR-Cas SystemsHumansPeptides, CyclicRNA, Guide, CRISPR-Cas SystemsSqualene MonooxygenaseU937 CellsmalforminsPeptides, CyclicRNA, Guide, CRISPR-Cas SystemsSqualene MonooxygenaseCRISPR/Cas9cytotoxicitymalforminpeptidessqualene epoxidase

Identifiers

PMID30734978
PMCPMC6618319
OpenAlexW2914201409

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.