Evidence map›Paper›PMID 33215742›Full record

ArticleThe EMBO journal2020

An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2.

Eunkyoung Shin, Hanyong Jin, Dae-Shik Suh, Yongyang Luo, Hye-Jeong Ha, Tae Heon Kim, Yoonsoo Hahn, Seogang Hyun, Kangseok Lee, Jeehyeon Bae

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2020. 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 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 8% 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

14 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
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  5. 5'-tRNANature communications · 2024
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  13. Response to Veitia et al.The EMBO journal · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Eunkyoung ShinSchool of Pharmacy, Chung-Ang University, Seoul, Korea.ORCID 0000-0002-3295-9000
Hanyong JinDepartment of Life Science, Chung-Ang University, Seoul, Korea.ORCID 0000-0002-5850-0791
Dae-Shik SuhDepartment of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Yongyang LuoSchool of Pharmacy, Chung-Ang University, Seoul, Korea.ORCID 0000-0001-5577-8977
Hye-Jeong HaSchool of Pharmacy, Chung-Ang University, Seoul, Korea.
Tae Heon KimDepartment of Pathology, Bundang CHA Hospital, CHA University, Seongnam, Korea.
Yoonsoo HahnDepartment of Life Science, Chung-Ang University, Seoul, Korea.ORCID 0000-0003-4273-9842
Seogang HyunDepartment of Life Science, Chung-Ang University, Seoul, Korea.ORCID 0000-0003-2008-0506
Kangseok LeeDepartment of Life Science, Chung-Ang University, Seoul, Korea.ORCID 0000-0002-0060-6884
Jeehyeon BaeSchool of Pharmacy, Chung-Ang University, Seoul, Korea.ORCID 0000-0003-1995-1378
Chung-Ang University · KRCHA University Bundang Medical Center · KRUlsan College · KR

Funding

National Research Foundation of Korea (NRF) 2019R1A2C2084563National Research Foundation of Korea (NRF) 2019R1H1A2080015National Research Foundation of Korea (NRF) NRF-2015R1A5A1008958National Research Foundation of Korea (NRF) NRF-2017R1A2B2011248National Research Foundation of Korea (NRF) NRF-2018R1A5A1025077
6 · The paper itself

Abstract

Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult-type granulosa cell tumors (AGCTs), introduces a target site for miR-1236, which causes haploinsufficiency of the tumor-suppressor FOXL2. This miR-1236-mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA-loaded RNA-induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and a mouse model of AGCT, abundance of the inversely regulated variant FOXL2 with miR-1236 levels is highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation-mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA-targeting disease-associated mutations in the CDS by forming a non-canonical miRISC.

Indexed as

MutationOpen Reading FramesAllelic ImbalanceAnimalsApoptosisArgonaute ProteinsCell DeathDEAD-box RNA HelicasesForkhead Box Protein L2Gene Expression Regulation, NeoplasticGene Knockout TechniquesGranulosa Cell TumorHEK293 CellsHumansMiceMice, KnockoutAGO3 protein, humanArgonaute ProteinsDEAD-box RNA HelicasesDHX9 protein, humanForkhead Box Protein L2FOXL2 protein, humanFoxl2 protein, mouseMicroRNAsMIRN1236 microRNA, humanNeoplasm ProteinsRNA, Messengerallelic imbalanceArgonaute3DHX9metastasismiR-1236

Identifiers

PMID33215742
PMCPMC7737606
OpenAlexW3098923172

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.