Evidence map›Paper›PMID 32705280›Full record

ArticleOncology reports2020

Retinoic acid induces differentiation in neuroblastoma via ROR1 by modulating retinoic acid response elements.

Abhinav Illendula, Norman Fultang, Bela Peethambaran

Open access · hybridAbstract read
In one paragraph

Article in Oncology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 25% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
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  8. Effects of Anionic Liposome Delivery of All-Biomimetics (Basel, Switzerland) · 2024
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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

3 authors at 1 institution in 1 country.

Abhinav IllendulaDepartment of Biology, University of The Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Norman FultangDepartment of Biology, University of The Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Bela PeethambaranDepartment of Biology, University of The Sciences in Philadelphia, Philadelphia, PA 19104, USA.
University of the Sciences · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroblastoma is the most common inheritable, solid neoplasm in children found under the age of 7 and accounts for approximately 7% of childhood cancers. A common treatment that has been prescribed for over a decade is retinoid therapy [using all‑trans retinoic acid (RA)]. Treatment with this differentiating agent has been revealed to progress the cells from their stem‑cell state to a mature neuronal state gaining classical neuronal characteristics, including the suppression of proliferation. However, the molecular mechanism underlying the action of RA treatment remains to be elucidated. In the present study, a novel mechanism of RA‑induced differentiation via regulation of receptor tyrosine kinase‑like orphan receptor 1 (ROR1) is reported. ROR1 is overexpressed in neuroblastoma but significantly downregulated in mature differentiated neurons. Hence, it was hypothesized that RA may modulate ROR1 leading to differentiation and termination of cancerous properties. Immunoblotting revealed that following RA treatment, ROR1 levels initially increased then sharply decreased by 96 h. This was paired with synaptophysin, a mature neuron marker, sharply increasing concurrently, providing evidence of differentiation by 96 h. Investigation of the ROR1 pathway confirmed ROR1‑dependent downstream activation of the PI3K/AKT signaling axis, a growth pathway previously demonstrated to promote differentiation. Chromatin immunoprecipitation revealed an increase in RAR binding to the promoters of ROR1 and its endogenous ligand, Wnt5a. This research provided compelling evidence that RA is able to modulate the expression of ROR1 and Wnt5a to promote differentiation through the expression of synaptophysin. This data combined with the overarching data from the scientific community regarding proliferation and other proliferative factors in early‑stage neurons provides a more in‑depth model of the process of differentiation in neurons.

Indexed as

Antineoplastic AgentsCell DifferentiationCell ProliferationChildDatasets as TopicGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansNeuroblastomaNeuronsPromoter Regions, GeneticReceptors, Retinoic AcidReceptor Tyrosine Kinase-like Orphan ReceptorsResponse ElementsSignal TransductionAntineoplastic AgentsReceptors, Retinoic AcidReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanSynaptophysinSYP protein, humanTretinoinWnt-5a ProteinWNT5A protein, humanall-trans retinoic aciddifferentiationneuroblastomareceptor tyrosine kinase-like orphan receptor 1retinoic acid response elementssynaptophysin

Identifiers

PMID32705280
PMCPMC7388440
OpenAlexW3039742835

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.