Evidence map›Paper›PMID 31822296›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

Arsenic sulfide induces RAG1-dependent DNA damage for cell killing by inhibiting NFATc3 in gastric cancer cells.

Ting Kang, Maolin Ge, Ruiheng Wang, Zhen Tan, Xiuli Zhang, Chuanying Zhu, Han Liu, Siyu Chen

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

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.8field-weighted citation impact, top 18% 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

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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

6 citing papers in PubMed, 24 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 3 institutions in 1 country.

Ting KangDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
Maolin GeState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, School of Medicine and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200025, China.
Ruiheng WangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, School of Medicine and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200025, China.
Zhen TanDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
Xiuli ZhangDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
Chuanying ZhuDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
Han LiuState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, School of Medicine and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200025, China. siyu.chen@shsmu.edu.cn.
Siyu ChenDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. liuhan68@sjtu.edu.cn.
Shanghai Jiao Tong University · CNXinHua Hospital · CNShanghai Institute of Hematology · CN

Funding

the National Key Research and Development Program of China 2018YFA0107802the National Natural Science Foundation of China 81274142the National Natural Science Foundation of China 81874353the National Natural Science Foundation of China 81973996the Science and Technology Commission of Shanghai Municipality 17401931300the Science and Technology Commission of Shanghai Municipality 19XD1402500the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant 20161304the Shanghai Municipal Health Commission 2019CXJQ01
6 · The paper itself

Abstract

backgroundArsenic sulfide was found to have potential anti-cancer activities, especially in gastric cancer. However, the underlying mechanism need to be further explored. This study was aimed to investigate the mechanism of arsenic compounds on gastric cancer.

methodsGastric cancer cell lines were infected with lentiviral vector carrying shNFATc3 and/or treated with arsenic sulfide. MTT assay were performed to assess cell growth. Flow cytometer assays were used to detect cell cycle and reactive oxygen species (ROS) level of gastric cancer cells. Western blot was carried out to detect nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3), cell cycle markers, DNA damage pathway protein expression as well as other protein expression in gastric cancer cell lines. The expression of recombination activating gene 1 (RAG1) in gastric cancer cell lines was determined by RNA-sequencing analyses and Real-Time qPCR. The effect of NFATc3 on RAG1 were determined by CHIP-qPCR assay. The effect of arsenic sulfide on AGS cells was evaluated in vivo.

resultsWe show that arsenic sulfide as well as knockdown of NFATc3 resulted in increased double-strand DNA damage in gastric cancer cells by increasing the expression of RAG1, an endonuclease essential for immunoglobulin V(D) J recombination. Overexpression of NFATc3 blocked the expression of RAG1 expression and DNA damage induced by arsenic sulfide. Arsenic sulfide induced cellular oxidative stress to redistribute NFATc3, thereby inhibiting its transcriptional function, which can be reversed by N-acetyl-L-cysteine (NAC). We show that NFATc3 targets the promoter of RAG1 for transcriptional inhibition. We further showed that NFATc3 upregulation and RAG1 downregulation significantly associated with poor prognosis in patients with gastric cancer. Our in vivo experiments further confirmed that arsenic sulfide exerted cytotoxic activity against gastric cancer cells through inhibiting NFATc3 to activate RAG1 pathway.

conclusionThese results demonstrate that arsenic sulfide targets NFATc3 to induce double strand DNA break (DSB) for cell killing through activating RAG1 expression. Our results link arsenic compound to the regulation of DNA damage control and RAG1 expression as a mechanism for its cytotoxic effect.

Indexed as

AnimalsArsenicalsCell Line, TumorCell ProliferationCell SurvivalGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansMiceNFATC Transcription FactorsPrognosisReactive Oxygen SpeciesSequence Analysis, RNAStomach NeoplasmsSulfidesXenograft Model Antitumor AssaysArsenicalsarsenic trisulfideHomeodomain ProteinsNFATC3 protein, humanNFATC Transcription FactorsRAG-1 proteinReactive Oxygen SpeciesSulfidesArsenic sulfideDNA damageGastric cancerNFATc3RAG1

Identifiers

PMID31822296
PMCPMC6902349
OpenAlexW2995058702

What OpenQuestion holds

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LicenceCC BY
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.