Evidence map›Paper›PMID 25889244›Full record

ArticleJournal of translational medicine2015

An RNA editing fingerprint of cancer stem cell reprogramming.

Leslie A Crews, Qingfei Jiang, Maria A Zipeto, Elisa Lazzari, Angela C Court, Shawn Ali, Christian L Barrett, Kelly A Frazer, Catriona H M Jamieson

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.0field-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

49 citing papers in PubMed, 59 citations in OpenAlex.

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  16. ADAR1 Isoforms RegulateInternational journal of molecular sciences · 2022
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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 2 institutions in 2 countries.

Leslie A CrewsDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. lcrews@ucsd.edu.
Qingfei JiangDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. q1jiang@ucsd.edu.
Maria A ZipetoDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. mzipeto@ucsd.edu.
Elisa LazzariDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. elazzari@ucsd.edu.
Angela C CourtDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. acourtrecart@ucsd.edu.
Shawn AliDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. sha003@ucsd.edu.
Christian L BarrettDivision of Genome Information Sciences, Department of Pediatrics, University of California, La Jolla, CA, 92093, USA. cbarrett@ucsd.edu.
Kelly A FrazerDivision of Genome Information Sciences, Department of Pediatrics, University of California, La Jolla, CA, 92093, USA. kafrazer@ucsd.edu.
Catriona H M JamiesonDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center at University of California, La Jolla, CA, 92093, USA. cjamieson@ucsd.edu.
University of California San Diego · USUniversity of Milan · IT

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
NCI NIH HHS CA130445NCI NIH HHS P30 CA023100NCI NIH HHS P30-CA023100
6 · The paper itself

Abstract

backgroundDeregulation of RNA editing by adenosine deaminases acting on dsRNA (ADARs) has been implicated in the progression of diverse human cancers including hematopoietic malignancies such as chronic myeloid leukemia (CML). Inflammation-associated activation of ADAR1 occurs in leukemia stem cells specifically in the advanced, often drug-resistant stage of CML known as blast crisis. However, detection of cancer stem cell-associated RNA editing by RNA sequencing in these rare cell populations can be technically challenging, costly and requires PCR validation. The objectives of this study were to validate RNA editing of a subset of cancer stem cell-associated transcripts, and to develop a quantitative RNA editing fingerprint assay for rapid detection of aberrant RNA editing in human malignancies.

methodsTo facilitate quantification of cancer stem cell-associated RNA editing in exons and intronic or 3'UTR primate-specific Alu sequences using a sensitive, cost-effective method, we established an in vitro RNA editing model and developed a sensitive RNA editing fingerprint assay that employs a site-specific quantitative PCR (RESSq-PCR) strategy. This assay was validated in a stably-transduced human leukemia cell line, lentiviral-ADAR1 transduced primary hematopoietic stem and progenitor cells, and in primary human chronic myeloid leukemia stem cells.

resultsIn lentiviral ADAR1-expressing cells, increased RNA editing of MDM2, APOBEC3D, GLI1 and AZIN1 transcripts was detected by RESSq-PCR with improved sensitivity over sequencing chromatogram analysis. This method accurately detected cancer stem cell-associated RNA editing in primary chronic myeloid leukemia samples, establishing a cancer stem cell-specific RNA editing fingerprint of leukemic transformation that will support clinical development of novel diagnostic tools to predict and prevent cancer progression.

conclusionsRNA editing quantification enables rapid detection of malignant progenitors signifying cancer progression and therapeutic resistance, and will aid future RNA editing inhibitor development efforts.

Indexed as

Cellular ReprogrammingAdenosine DeaminaseBiomarkers, TumorBlast CrisisCoculture TechniquesDisease ProgressionHumansK562 CellsLentivirusLeukemia, Myelogenous, Chronic, BCR-ABL PositiveModels, BiologicalNeoplastic Stem CellsReproducibility of ResultsRNA EditingAdenosine DeaminaseBiomarkers, Tumor

Identifiers

PMID25889244
PMCPMC4341880
OpenAlexW2102015716

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.