Evidence map›Paper›PMID 29475734›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018

miR-145 Antagonizes SNAI1-Mediated Stemness and Radiation Resistance in Colorectal Cancer.

Yun Zhu, Cindy Wang, Scott A Becker, Katie Hurst, Lourdes M Nogueira, Victoria J Findlay, E Ramsay Camp

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 4% 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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Yun ZhuDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: zhuyun@musc.edu.
Cindy WangDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Scott A BeckerDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Katie HurstDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Lourdes M NogueiraDepartment of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Victoria J FindlayDepartment of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
E Ramsay CampDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: campe@musc.edu.
Medical University of South Carolina · USMUSC Hollings Cancer Center · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Jian Ouyang · 2009 to 2026
$42.7M
South Carolina Cancer Disparities Research Center (SC CADRE)U54CA210962 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI FORD, MARVELLA ELIZABETH, SALLEY, JUDITH · 2017 to 2023
$6.7M
South Carolina Cancer Disparities Research Center (SC CaDRe)U54CA210963 · NCI · SOUTH CAROLINA STATE UNIVERSITY · PI FORD, MARVELLA ELIZABETH, SALLEY, JUDITH · 2017 to 2023
$6.1M
NCI NIH HHS P30 CA138313NCI NIH HHS U54 CA210962NCI NIH HHS U54 CA210963
6 · The paper itself

Abstract

Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells. Using a miR-145 luciferase reporter assay, we determined that ectopic SNAI1 expression significantly repressed the miR-145 promoter. DLD1-SNAI1 and HCT116-SNAI1 cells demonstrated decreased RT sensitivity and, conversely, miR-145 replacement significantly enhanced RT sensitivity. Of the five parental colon cancer cell lines, SW620 cells demonstrated relatively high endogenous SNAI1 and low miR-145 levels. In the SW620 cells, miR-145 replacement decreased CSC-related transcription factor expression, spheroid formation, and radiation resistance. In rectal cancer patient-derived xenografts, CSC identified by EpCAM+/aldehyde dehydrogenase (ALDH)+ demonstrated high expression of SNAI1, c-Myc, and Nanog compared with non-CSCs (EpCAM+/ALDH-). Conversely, patient-derived CSCs demonstrated low miR-145 expression levels relative to non-CSCs. These results suggest that the SNAI1:miR-145 pathway represents a novel therapeutic target in colorectal cancer to overcome RT resistance.

Indexed as

BiomarkersCell Line, TumorCell Self RenewalColorectal NeoplasmsGene Expression Regulation, NeoplasticHumansMicroRNAsModels, BiologicalNeoplastic Stem CellsPhenotypePromoter Regions, GeneticRadiation ToleranceRNA InterferenceSnail Family Transcription FactorsBiomarkersMicroRNAsMIRN145 microRNA, humanSNAI1 protein, humanSnail Family Transcription Factorscolorectal cancermicroRNA-145radiationresistanceSNAI1stem cell

Identifiers

PMID29475734
PMCPMC5910672
OpenAlexW2781949851

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.