Evidence map›Paper›PMID 28459431›Full record

ArticleOncogenesis2017

miRNA-34c-5p inhibits amphiregulin-induced ovarian cancer stemness and drug resistance via downregulation of the AREG-EGFR-ERK pathway.

S-L Tung, W-C Huang, F-C Hsu, Z-P Yang, T-H Jang, J-W Chang, C-M Chuang, C-R Lai, L-H Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 2 pooled it
4.4field-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

65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.

  1. Pooled it
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  18. The role of amphiregulin in ovarian function and disease.Cellular and molecular life sciences : CMLS · 2023
    Review
  19. Article
  20. Molecular mechanism of CD163Annals of translational medicine · 2022
    Article

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

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 4 institutions in 1 country.

S-L TungInstitute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
W-C HuangInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
F-C HsuInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
Z-P YangInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
T-H JangInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
J-W ChangInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
C-M ChuangInstitute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
C-R LaiSection of Cytopathology, Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
L-H WangInstitute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
National Health Research Institutes · TWNational Tsing Hua University · TWNational Yang Ming Chiao Tung University · TWTaipei Veterans General Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial ovarian cancer is the most lethal gynecological cancer mainly due to late diagnosis, easy spreading and rapid development of chemoresistance. Cancer stem cells are considered to be one of the main mechanisms for chemoresistance, as well as metastasis and recurrent disease. To explore the stemness characteristics of ovarian cancer stem cells, we successfully enriched ovarian cancer stem-like cells from an established ovarian cancer cell line (SKOV-I6) and a fresh ovarian tumor-derived cell line (OVS1). These ovarian cancer stem-like cells possess important cancer stemness characteristics including sphere-forming and self-renewing abilities, expressing important ovarian cancer stem cell and epithelial-mesenchymal transition markers, as well as increased drug resistance and potent tumorigenicity. Microarray analysis of OVS1-derived sphere cells revealed increased expression of amphiregulin (AREG) and decreased expression of its conserved regulatory microRNA, miR-34c-5p, when compared with the OVS1 parental cells. Overexpression of AREG and decreased miR-34c-5p expression in SKOV-I6 and OVS1 sphere cells were confirmed by quantitative real-time PCR analysis. Luciferase reporter assay and mutant analysis confirmed that AREG is a direct target of miR-34c-5p. Furthermore, AREG-mediated increase of sphere formation, drug resistance toward docetaxel and carboplatin, as well as tumorigenicity of SKOV-I6 and OVS1 cells could be abrogated by miR-34c-5p. We further demonstrated that miR-34c-5p inhibited ovarian cancer stemness through downregulation of the AREG-EGFR-ERK pathway. Overexpression of AREG was found to be correlated with advanced ovarian cancer stages and poor prognosis. Taken together, our data suggest that AREG promotes ovarian cancer stemness and drug resistance via the AREG-EGFR-ERK pathway and this is inhibited by miR-34c-5p. Targeting AREG, miR-34c-5p could be a potential strategy for anti-cancer-stem cell therapy in ovarian cancer.

Identifiers

PMID28459431
PMCPMC5525454
OpenAlexW2610956165

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LicenceCC BY
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Registered trials

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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.