Evidence map›Paper›PMID 31110284›Full record

ArticleScientific reports2019

A gapmer antisense oligonucleotide targeting SRRM4 is a novel therapeutic medicine for lung cancer.

Masahito Shimojo, Yuuya Kasahara, Masaki Inoue, Shin-Ichi Tsunoda, Yoshie Shudo, Takayasu Kurata, Satoshi Obika

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

28 citing papers in PubMed, 43 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

7 authors at 4 institutions in 1 country.

Masahito ShimojoGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. shimojo@phs.osaka-u.ac.jp.ORCID http://orcid.org/0000-0003-1859-4444
Yuuya KasaharaGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Masaki InoueNational Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Shin-Ichi TsunodaNational Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.ORCID http://orcid.org/0000-0003-3299-2182
Yoshie ShudoKansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan.
Takayasu KurataKansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan.
Satoshi ObikaGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.ORCID http://orcid.org/0000-0002-6842-6812
Kansai Medical University · JPKobe Gakuin University · JPNational Institute of Biomedical Innovation, Health and Nutrition · JPThe University of Osaka · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small cell lung cancer (SCLC) is the most aggressive neuroendocrine phenotype of the deadliest human lung cancers. However the therapeutic landscape for SCLC has not changed in over 30 years. Effective treatment and prognosis are needed to combat this aggressive cancer. Herein we report that Ser/Arg repetitive matrix 4 (SRRM4), a splicing activator, is abnormally expressed at high levels in SCLC and thus is a potential therapeutic target. We screened an effective gapmer antisense oligonucleotide (gASO) targeting SRRM4 in vitro which led to cell death of SCLC. Our gASO, which is stabilized by containing artificial nucleotides, effectively represses SRRM4 mRNA. We found that our gASO repressed SRRM4 synthesis leading to a dramatic tumor reduction in a lung cancer mouse model. We also analyzed miRNA microarray and found that the miR-4516 is abnormally increased in exosomes in the blood of SCLC patients. Treating with gASO suppressed tumors in the SCLC model mouse concurrently reduced plasma miR-4516. In conclusion this study reports that administration of an SRRM4-targeted gASO coupled with a novel miRNA diagnostic methodology represents a potential breakthrough in the therapeutic treatment of high mortality SCLC.

Indexed as

A549 CellsAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansLung NeoplasmsMaleMCF-7 CellsMiceMice, Inbred BALB CMice, NudeMicroRNAsNerve Tissue ProteinsOligonucleotides, AntisensePrognosisRNA, MessengerMicroRNAsNerve Tissue ProteinsOligonucleotides, AntisenseRNA, MessengerSRRM4 protein, human

Identifiers

PMID31110284
PMCPMC6527545
OpenAlexW2946249528

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.