Evidence map›Paper›PMID 32914209›Full record

ArticleCellular and molecular life sciences : CMLS2021

NEAT1 polyA-modulating antisense oligonucleotides reveal opposing functions for both long non-coding RNA isoforms in neuroblastoma.

Alina Naveed, Jack A Cooper, Ruohan Li, Alysia Hubbard, Jingwei Chen, Tao Liu, Steve D Wilton, Sue Fletcher, Archa H Fox

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.4field-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

48 citing papers in PubMed, 70 citations in OpenAlex.

  1. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
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  11. NONO Maintains SREBP-Regulated Cholesterol Biosynthesis via RNA Binding in Neuroblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  12. Review
  13. Review
  14. Article
  15. Article
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  17. Biology methods & protocols · 2025
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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

9 authors at 3 institutions in 1 country.

Alina NaveedSchool of Human Sciences and School of Molecular Sciences, The University of Western Australia, Crawley, WA, 6009, Australia.ORCID http://orcid.org/0000-0002-1820-9908
Jack A CooperSchool of Human Sciences and School of Molecular Sciences, The University of Western Australia, Crawley, WA, 6009, Australia.ORCID http://orcid.org/0000-0001-6523-8624
Ruohan LiSchool of Human Sciences and School of Molecular Sciences, The University of Western Australia, Crawley, WA, 6009, Australia.ORCID http://orcid.org/0000-0002-7037-8469
Alysia HubbardCentre for Microscopy, Characterisation and Analysis, The University of Western Australia, Crawley, WA, 6009, Australia.
Jingwei ChenChildren's Cancer Institute Australia, Randwick, NSW, 2031, Australia.
Tao LiuChildren's Cancer Institute Australia, Randwick, NSW, 2031, Australia.
Steve D WiltonCentre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, 6150, Australia.ORCID http://orcid.org/0000-0002-9400-893X
Sue FletcherCentre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, 6150, Australia.ORCID http://orcid.org/0000-0002-8632-641X
Archa H FoxSchool of Human Sciences and School of Molecular Sciences, The University of Western Australia, Crawley, WA, 6009, Australia. archa.fox@uwa.edu.au.ORCID http://orcid.org/0000-0003-1962-270X
The University of Western Australia · AUMurdoch University · AUUNSW Sydney · AU

Funding

Australian Research Council FT180100204Cancer Council Western Australia APP1106644Cancer Council Western Australia APP1126667National Health and Medical Research Council APP1147496
6 · The paper itself

Abstract

Many long non-coding RNAs (lncRNA) are highly dysregulated in cancer and are emerging as therapeutic targets. One example is NEAT1, which consists of two overlapping lncRNA isoforms, NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb), that are functionally distinct. The longer NEAT1_2 is responsible for scaffolding gene-regulatory nuclear bodies termed paraspeckles, whereas NEAT1_1 is involved in paraspeckle-independent function. The NEAT1 isoform ratio is dependent on the efficient cleavage and polyadenylation of NEAT1_1 at the expense of NEAT1_2. Here, we developed a targeted antisense oligonucleotide (ASO) approach to sterically block NEAT1_1 polyadenylation processing, achieving upregulation of NEAT1_2 and abundant paraspeckles. We have applied these ASOs to cells of the heterogeneous infant cancer, neuroblastoma, as we found higher NEAT1_1:NEAT1_2 ratio and lack of paraspeckles in high-risk neuroblastoma cells. These ASOs decrease NEAT1_1 levels, increase NEAT1_2/paraspeckles and concomitantly reduce cell viability in high-risk neuroblastoma specifically. In contrast, overexpression of NEAT1_1 has the opposite effect, increasing cell proliferation. Transcriptomic analyses of high-risk neuroblastoma cells with altered NEAT1 ratios and increased paraspeckle abundance after ASO treatment showed an upregulation of differentiation pathways, as opposed to the usual aggressive neuroblastic phenotype. Thus, we have developed potential anti-cancer ASO drugs that can transiently increase growth-inhibiting NEAT1_2 RNA at the expense of growth-promoting NEAT1_1 RNA. These ASOs, unlike others that degrade lncRNAs, provide insights into the importance of altering lncRNA polyadenylation events to suppress tumorigenesis as a strategy to combat cancer.

Indexed as

Gene Expression Regulation, NeoplasticCell Line, TumorCohort StudiesGene Expression ProfilingHumansKaplan-Meier EstimateNeuroblastomaOligonucleotides, AntisensePoly ARNA IsoformsRNA, Long NoncodingNEAT1 long non-coding RNA, humanOligonucleotides, AntisensePoly ARNA IsoformsRNA, Long NoncodingBiomolecular condensatesMYCNNONORNA therapeuticsSuper resolution

Identifiers

PMID32914209
PMCPMC11073103
OpenAlexW3084708630

What OpenQuestion holds

Textmetadata
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.