Evidence map›Paper›PMID 25304376›Full record

ArticleCancer letters2015

Disruption of microRNA-21 by TALEN leads to diminished cell transformation and increased expression of cell-environment interaction genes.

Buyuan Chen, Xinji Chen, Xiwei Wu, Xiaoling Wang, Yingjia Wang, Ting-Yu Lin, Jessica Kurata, Jun Wu, Steven Vonderfecht, Guihua Sun and 4 more

Open access · greenAbstract read
In one paragraph

Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 23% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  6. Article
  7. Identification of the Potential Molecular Mechanism ofComputational and mathematical methods in medicine · 2022
    Article
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  18. MiR-21: an environmental driver of malignant melanoma?Journal of translational medicine · 2015
    Review
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

14 authors at 4 institutions in 2 countries.

Buyuan Chen *Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Xinji Chen *Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Xiwei WuDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Xiaoling WangDepartment of Virology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Yingjia WangDepartment of Virology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Ting-Yu LinDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Jessica KurataDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Jun WuDivision of Comparative Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA.
Steven VonderfechtDivision of Comparative Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA.
Guihua SunDepartment of Diabetes & Metabolic Diseases, Beckman Research Institute of City of Hope, Duarte, California, USA.
He HuangBone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Jiing-Kuan YeeDepartment of Virology, Beckman Research Institute of City of Hope, Duarte, California, USA.
Jianda HuFujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Ren-Jang LinDepartment of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
City of Hope · USCity Of Hope National Medical Center · USFujian Medical University · CNFirst Affiliated Hospital Zhejiang University · CN

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
NCI NIH HHS P30 CA033572NCI NIH HHS P30-CA033572
6 · The paper itself

Abstract

MicroRNA-21 is dysregulated in many cancers and fibrotic diseases. Since miR-21 suppresses several tumor suppressor and anti-apoptotic genes, it is considered a cancer therapeutic target. Antisense oligonucleotides are commonly used to inhibit a miRNA; however, blocking miRNA function via an antagomir is temporary, often only achieves a partial knock-down, and may be complicated by off-target effects. Here, we used transcription activator-like effector nucleases (TALENs) to disrupt miR-21 in cancerous cells. Individual deletion clones were screened and isolated without drug selection. Sequencing and quantitative RT-PCR identified clones with no miR-21 expression. The loss of miR-21 led to subtle but global increases of mRNAs containing miR-21 target sequences. Cells without miR-21 became more sensitive to cisplatin and less transformed in culture and in mouse xenografts. In addition to the increase of PDCD4 and PTEN protein, mRNAs for COL4A1, JAG1, SERPINB5/Maspin, SMAD7, and TGFBI - all are miR-21 targets and involved in TGFβ and fibrosis regulation - were significantly upregulated in miR-21 knockout cells. Gene ontology and pathway analysis suggested that cell-environment interactions involving extracellular matrix can be an important miR-21 pathogenic mechanism. The study also demonstrates the value of using TALEN-mediated microRNA gene disruption in human pathobiological studies.

Indexed as

AnimalsBiomarkers, TumorCell Transformation, NeoplasticEndonucleasesFemaleHigh-Throughput Nucleotide SequencingHumansMiceMice, Inbred NODMice, SCIDMicroRNAsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTranscriptional ActivationTranscription FactorsBiomarkers, TumorEndonucleasesMicroRNAsMIRN21 microRNA, humanRNA, MessengerTranscription Factorscancerextracellular matrixgene editingmicroRNAmiR-21TALEN

Identifiers

PMID25304376
PMCPMC4615566
OpenAlexW1964614301

What OpenQuestion holds

Textmetadata
LicenceTDM
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.