Evidence map›Paper›PMID 37789102›Full record

ArticleBritish journal of cancer2023

Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.

Shivani Bailey, Marta Ferraresso, Luz Alonso-Crisostomo, Dawn Ward, Stephen Smith, James C Nicholson, Harpreet Saini, Anton J Enright, Cinzia G Scarpini, Nicholas Coleman and 1 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2023. 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 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  7. Article
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  11. MicroRNAs in Testicular Germ Cell Tumors: The Teratoma Challenge.International journal of molecular sciences · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Shivani BaileyDepartment of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Marta FerraressoDepartment of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Luz Alonso-CrisostomoDepartment of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Dawn WardDepartment of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Stephen SmithDepartment of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.ORCID 0000-0001-7744-3238
James C NicholsonDepartment of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK.
Harpreet SainiEMBL-European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Anton J EnrightDepartment of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Cinzia G Scarpini *Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Nicholas Coleman *Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK. nc109@cam.a.cuk.
Matthew J Murray *Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK. mjm16@cam.ac.uk.ORCID 0000-0002-4480-1147
University of Cambridge · GBEuropean Bioinformatics Institute · GB

Funding

Cancer Research UKDepartment of Health BRC-1215-20014
6 · The paper itself

Abstract

backgroundMiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed sequence 'AAGUGC', determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally.

methodsWe targeted miR-371~373 and/or miR-302/367 clusters in malignant GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcript inhibition, and peptide nucleic acid (PNA) or locked nucleic acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays.

resultsMiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant GCT cells, regardless of subtype (seminoma/YST/EC). Following the unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with the de-repression of multiple mRNAs targeted by AAGUGC seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signalling, vesicle organisation/transport, and cell cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell cycle effects, with an increase of cells in G0/G1-phase and a decrease in S-phase.

conclusionTargeting of specific miR-371~373 and miR-302/367 microRNAs in malignant GCTs demonstrated their functional significance, with growth inhibition mediated through cell cycle disruption.

Indexed as

MicroRNAsNeoplasms, Germ Cell and EmbryonalSeminomaTesticular NeoplasmsAdultCell CycleChildDNAHumansMaleDNAMicroRNAsMIRN371 microRNA, human

Identifiers

PMID37789102
PMCPMC10628203
OpenAlexW4387303020

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.