Evidence map›Paper›PMID 33718136›Full record

ArticleFrontiers in oncology2021

Epigenetic Silencing of STAT3-Targeted miR-193a, by Constitutive Activation of JAK/STAT Signaling, Leads to Tumor Progression Through Overexpression of YWHAZ in Gastric Cancer.

Kuo-Liang Wei, Jian-Liang Chou, Yin-Chen Chen, Jie-Ting Low, Guan-Ling Lin, Jing-Lan Liu, Te-Sheng Chang, Wei-Ming Chen, Yung-Yu Hsieh, Pearlly S Yan and 7 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 32% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Epigenetic alterations inJournal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025
    Review
  5. Article
  6. 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

17 authors at 3 institutions in 2 countries.

Kuo-Liang WeiDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Jian-Liang ChouDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Yin-Chen ChenDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Jie-Ting LowDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Guan-Ling LinDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Jing-Lan LiuDepartment of Anatomical Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Te-Sheng ChangDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Wei-Ming ChenDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Yung-Yu HsiehDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Pearlly S YanDivision of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
Yu-Ming ChuangDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Jora M J LinDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Shu-Fen WuDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Ming-Ko ChiangDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Chin LiDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
Cheng-Shyong WuDivision of Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Michael W Y ChanDepartment of Biomedical Sciences, National Chung Cheng University, Chiayi, Taiwan.
National Chung Cheng University · TWChiayi Chang Gung Memorial Hospital · TWThe Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Ultra-Low and Single-Cell Transcriptome Analysis in Patient-Derived Rare CLL Precursor CellsR50CA211524 · NCI · OHIO STATE UNIVERSITY · PI YAN, PEARLLY · 2016 to 2020
$745k
NCI NIH HHS P30 CA016058NCI NIH HHS R50 CA211524
6 · The paper itself

Abstract

purposeThe purpose of this study was to identify genes that were epigenetically silenced by STAT3 in gastric cancer.

methodsMBDcap-Seq and expression microarray were performed to identify genes that were epigenetically silenced in AGS gastric cancer cell lines depleted of STAT3. Cell lines and animal experiments were performed to investigate proliferation and metastasis of miR-193a and YWHAZ in gastric cancer cell lines. Bisulfite pyrosequencing and tissue microarray were performed to investigate the promoter methylation of miR-193a and expression of STAT3, YWHAZ in patients with gastritis (n = 8) and gastric cancer (n = 71). Quantitative methylation-specific PCR was performed to examine miR-193a promoter methylation in cell-free DNA of serum samples in gastric cancer patients (n = 19).

resultsAs compared with parental cells, depletion of STAT3 resulted in demethylation of a putative STAT3 target, miR-193a, in AGS gastric cancer cells. Although bisulfite pyrosequencing and epigenetic treatment confirmed that miR-193a was epigenetically silenced in gastric cancer cell lines, ChIP-PCR found that it may be indirectly affected by STAT3. Ectopic expression of miR-193a in AGS cells inhibited proliferation and migration of gastric cancer cells. Further expression microarray and bioinformatics analysis identified YWHAZ as one of the target of miR-193a in AGS gastric cancer cells, such that depletion of YWHAZ reduced migration in AGS cells, while its overexpression increased invasion in MKN45 cells

conclusionsConstitutive activation of JAK/STAT signaling may confer epigenetic silencing of the STAT3 indirect target and tumor suppressor microRNA, miR-193a in gastric cancer. Transcriptional suppression of miR-193a may led to overexpression of YWHAZ resulting in tumor progression. Targeted inhibition of STAT3 may be a novel therapeutic strategy against gastric cancer.

Indexed as

epigeneticsgastric cancermiR-193aSTAT3YWHAZ

Identifiers

PMID33718136
PMCPMC7951088
OpenAlexW3134677395

What OpenQuestion holds

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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.