Evidence map›Paper›PMID 34796468›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2021

Upregulation of TTYH3 promotes epithelial-to-mesenchymal transition through Wnt/β-catenin signaling and inhibits apoptosis in cholangiocarcinoma.

Weijie Xue, Bingzi Dong, Yanjie Zhao, Yixiu Wang, Chenyu Yang, Yuwei Xie, Zhaojian Niu, Chengzhan Zhu

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
14.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

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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

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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

28 citing papers in PubMed, 71 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Weijie Xue *Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, 266003, Qingdao, People's Republic of China.
Bingzi Dong *Shandong Key Laboratory of Digital Medicine and Computer Assisted Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, 266003, Qingdao, China.
Yanjie ZhaoSchool of Public Health, Qingdao University, Qingdao, China.
Yixiu WangDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, 266003, Qingdao, China.
Chenyu YangDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, China.
Yuwei XieDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, 266003, Qingdao, China.
Zhaojian NiuDepartment of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, 266003, Qingdao, People's Republic of China. nzj532@126.com.
Chengzhan ZhuShandong Key Laboratory of Digital Medicine and Computer Assisted Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, 266003, Qingdao, China. zhuchengz@qduhospital.cn.ORCID http://orcid.org/0000-0002-2775-5863
Qingdao University · CN

Funding

National Natural Science Foundation of China 81600490postdoctoral research foundation of china 2016M602098qingdao postdoctoral science foundation 2016046shandong higher education young science and technology support program 2020KJL005taishan scholar foundation of shandong province 2019010668
6 · The paper itself

Abstract

purposeCholangiocarcinoma (CCA) is a highly invasive malignant tumor originating from the bile duct epithelium. Tweety homolog 3 (TTYH3) is a member of the family of calcium-activated chloride channels, which have several biological functions. Here, we aimed to investigate the expression and biological function of TTYH3 in CCA.

methodsThe mRNA and protein expression levels of TTYH3 were investigated in primary human CCA tissues and normal tissues. The DNA methylation levels of three CpG sites in the TTYH3 promoter region were evaluated using pyrosequencing. The effect of TTYH3 expression on proliferation, apoptosis, migration and invasion were assessed in HUCCT1 and QBC939 cells. Xenograft models were developed to substantiate its role in the development of CCA. Western blot analysis was used to investigate the mechanistic role of TTYH3 in regulating CCA progression.

resultsWe found that TTYH3 was highly expressed both at the mRNA and protein levels in CCA (p = 0.0001) and that the expression levels were significantly related to a poor overall survival of the patients (p = 0.0019). The DNA methylation levels of three CpG sites in the TTYH3 promoter region were significantly lower in CCA tissues compared to normal tissues (p < 0.05). In vitro studies indicated that TTYH3 can promote the proliferation, migration and invasion of the CCA cells. TTYH3 overexpression significantly promoted tumor progression and cellular proliferation in vivo as indicated by Ki-67 expression. In addition, we found that exogenous TTYH3 overexpression induced epithelial-mesenchymal transition (EMT) in CCA as indicated by expression changes in E-cadherin, N-cadherin and vimentin. The EMT process was found to occur through the Wnt/β-catenin signaling pathway, with simultaneous changes in P-GSK3β and β-catenin levels.

conclusionsOur data indicate that DNA hypomethylation-induced overexpression of TTYH3 regulates CCA development and metastasis through the Wnt/β-catenin pathway.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaAnimalsApoptosisbeta CateninBile Ducts, IntrahepaticCell Line, TumorCell MovementCell ProliferationChloride ChannelsEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansUp-RegulationWnt Signaling Pathwaybeta CateninChloride ChannelsTTYH3 protein, humanCholangiocarcinomaDNA methylationEpithelial-mesenchymal transitionMigrationProliferationTTYH3Wnt/β-catenin

Identifiers

PMID34796468
PMCPMC12980733
OpenAlexW3213951496

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.