Evidence map›Paper›PMID 28981911›Full record

ArticleNucleic acids research2017

Naturally existing isoforms of miR-222 have distinct functions.

Feng Yu, Katherine A Pillman, Corine T Neilsen, John Toubia, David M Lawrence, Anna Tsykin, Michael P Gantier, David F Callen, Gregory J Goodall, Cameron P Bracken

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

47 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  4. IsomiR Utility in Amyotrophic Lateral Sclerosis Prognostication.medRxiv : the preprint server for health sciences · 2025
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  5. Article
  6. IsomiRome analysis reveals dysregulation of 5' isomiRs during SARS-CoV-2 infection.Computational and structural biotechnology journal · 2025
    Article
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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

10 authors at 4 institutions in 1 country.

Feng YuCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
Katherine A PillmanCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
Corine T NeilsenSchool of Health, Medical and Applied Sciences, Central Queensland University, Queensland 4000, Australia.
John ToubiaCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
David M LawrenceCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
Anna TsykinCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
Michael P GantierCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
David F CallenSchool of Medicine, Discipline of Medicine, University of Adelaide, SA 5000, Australia.
Gregory J GoodallCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
Cameron P BrackenCentre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia.
South Australia Pathology · AUCentral Queensland University · AUHudson Institute of Medical Research · AUThe University of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deep-sequencing reveals extensive variation in the sequence of endogenously expressed microRNAs (termed 'isomiRs') in human cell lines and tissues, especially in relation to the 3' end. From the immunoprecipitation of the microRNA-binding protein Argonaute and the sequencing of associated small RNAs, we observe extensive 3'-isomiR variation, including for miR-222 where the majority of endogenously expressed miR-222 is extended by 1-5 nt compared to the canonical sequence. We demonstrate this 3' heterogeneity has dramatic implications for the phenotype of miR-222 transfected cells, with longer isoforms promoting apoptosis in a size (but not 3' sequence)-dependent manner. The transfection of longer miR-222 isomiRs did not induce an interferon response, but did downregulate the expression of many components of the pro-survival PI3K-AKT pathway including PIK3R3, a regulatory subunit whose knockdown phenocopied the expression of longer 222 isoforms in terms of apoptosis and the inhibition of other PI3K-AKT genes. As this work demonstrates the capacity for 3' isomiRs to mediate differential functions, we contend more attention needs to be given to 3' variance given the prevalence of this class of isomiR.

Indexed as

Gene Expression RegulationApoptosisCell LineCell Line, TumorCell ProliferationHumansImmunoblottingMCF-7 CellsMicroRNAsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA IsoformsSignal TransductionMicroRNAsMIR222, humanPhosphatidylinositol 3-KinasesPIK3R3 protein, humanProto-Oncogene Proteins c-aktRNA Isoforms

Identifiers

PMID28981911
PMCPMC5737821
OpenAlexW2755276619

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.