Evidence map›Paper›PMID 38082327›Full record

ArticleJournal of translational medicine2023

Bufalin targeting CAMKK2 inhibits the occurrence and development of intrahepatic cholangiocarcinoma through Wnt/β-catenin signal pathway.

Huhu Zhang, Xiaolei Dong, Xiaoyan Ding, Guoxiang Liu, Fanghao Yang, Qinghang Song, Hongxiao Sun, Guang Chen, Shuang Li, Ya Li and 5 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

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  6. Bufalin Inhibits the PI3K/AKT Pathway by Targeting GTF3C4 to Impede Breast Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

15 authors at 2 institutions in 1 country.

Huhu Zhang *Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Xiaolei Dong *Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Xiaoyan DingDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Guoxiang LiuDepartment of Clinical Laboratory, Weifang People's Hospital, 151, Guangwen Street, Weifang, 261041, China.
Fanghao YangDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Qinghang SongHealth Science Center, Qingdao University, Qingdao, 266071, China.
Hongxiao SunHeart Center, Women and Children's Hospital, Qingdao University, 6, Tongfu Road, Qingdao, 266034, China.
Guang ChenDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Shuang LiDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Ya LiDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Mengjun WangDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Tingting GuoHealth Science Center, Qingdao University, Qingdao, 266071, China.
Zhe ZhangDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China.
Bing LiDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China. libing_516@qdu.edu.cn.
Lina YangDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266071, China. yanglina@qdu.edu.cn.ORCID 0009-0009-8668-0433
Qingdao University · CNWeifang People's Hospital · CN

Funding

China Postdoctoral Science Foundation No.2020M682131China Postdoctoral Science Foundation No.2021T140357National Natural Science Foundation of China No.81803895Shandong Province Natural Science Foundation ZR2021YQ57
6 · The paper itself

Abstract

backgroundIntrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes and therapeutic drug. Here, we studied that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the occurrence and metastasis of intrahepatic cholangiocarcinoma through Wnt/β-catenin signal pathway.

methodsIC50 of bufalin in ICC cells was determined by CCK8 and invasive and migratory abilities were verified by wound healing, cell cloning, transwell and Western blot. IF and IHC verified the expression of CAMKK2 between ICC patients and normal subjects. BLI and pull-down demonstrated the binding ability of bufalin and CAMKK2. Bioinformatics predicted whether CAMKK2 was related to the Wnt/β-catenin pathway. SKL2001, an activator of β-catenin, verified whether bufalin acted through this pathway. In vitro and in vivo experiments verified whether overexpression of CAMKK2 affects the proliferative and migratory effects of ICC. Transmission electron microscopy verified mitochondrial integrity. Associated Ca

resultsIt was found that bufalin inhibited the proliferation and migration of ICC, and CAMKK2 was highly expressed in ICC, and its high expression was positively correlated with poor prognosis.CAMKK2 is a direct target of bufalin, and is associated with the Wnt/β-catenin signaling pathway, which was dose-dependently decreased after bufalin treatment. In vitro and in vivo experiments verified that CAMKK2 overexpression promoted ICC proliferation and migration, and bufalin reversed this effect. CAMKK2 was associated with Ca

conclusionsOur results suggest that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the proliferation and migration of intrahepatic cholangiocarcinoma through Wnt/β-catenin signal pathway. Thus, bufalin, as a drug, may also be used for cancer therapy in ICC in the future.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaMitochondrial Diseasesbeta CateninBile Ducts, IntrahepaticBufanolidesCalcium-Calmodulin-Dependent Protein Kinase KinaseCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansWnt Signaling Pathwaybeta CateninbufalinBufanolidesCalcium-Calmodulin-Dependent Protein Kinase KinaseCAMKK2 protein, humanANXA2BufalinCa2+CAMKK2Intrahepatic cholangiocarcinomaMigrationMitochondrial dysfunctionProliferation

Identifiers

PMID38082327
PMCPMC10714474
OpenAlexW4389573566

What OpenQuestion holds

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LicenceCC BY
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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.