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Published in: Pathology & Oncology Research 2/2019

01-04-2019 | Original Article

Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer

Authors: Yanan Pang, Zhiyong Liu, Shanrong Liu

Published in: Pathology & Oncology Research | Issue 2/2019

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Abstract

Arsenic trioxide is an approved chemotheraputic agent for the treatment of acute promyelocytic leukemia (APL). Recently, numerous studies suggested that arsenic trioxide acts as anti-cancer roles in various human malignancies. However, the molecular mechanisms are not fully elucidated. In this study, we explored the critical targets of arsenic trioxide and their interaction network systematically by searching the publicly available published database like DrugBank (DB) and STRING. Seven direct protein targets (DPTs) and 111 DPT-associated genes were identified. The enrichment analysis of arsenic trioxide associated genes/proteins revealed 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Among these pathways, phosphatidylinositol-4,5-bisphosphate-3-kinase -Akt (PI3K-Akt) single pathway and pancreatic cancer pathway are highly correlated with arsenic trioxide and have 5 overlapped targets. Then we investigated the gene alternation of selected critical genes in pancreatic cancer studies using cBio portal. These results indicated that arsenic trioxide could act anti-tumor function through PI3K-Akt single pathway and identified critical genes might be therapeutic targets for pancreatic cancer.
Literature
2.
go back to reference Wang ZG, Rivi R, Delva L, König A, Scheinberg DA, Gambacorti-Passerini C, Gabrilove JL, Warrell RP Jr, Pandolfi PP (1998) Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Blood 92(5):1497–1504PubMed Wang ZG, Rivi R, Delva L, König A, Scheinberg DA, Gambacorti-Passerini C, Gabrilove JL, Warrell RP Jr, Pandolfi PP (1998) Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Blood 92(5):1497–1504PubMed
5.
go back to reference Yang MH, Zang YS, Huang H, Chen K, Li B, Sun GY, Zhao XW (2014) Arsenic trioxide exerts anti-lung cancer activity by inhibiting angiogenesis. Curr Cancer Drug Targets 14(6):557–566CrossRefPubMed Yang MH, Zang YS, Huang H, Chen K, Li B, Sun GY, Zhao XW (2014) Arsenic trioxide exerts anti-lung cancer activity by inhibiting angiogenesis. Curr Cancer Drug Targets 14(6):557–566CrossRefPubMed
7.
go back to reference Gao JK, Wang LX, Long B, Ye XT, Su JN, Yin XY, Zhou XX, Wang ZW (2015) Arsenic trioxide inhibits cell growth and invasion via Down- regulation of Skp2 in pancreatic Cancer cells. Asian Pac J Cancer Prev 16(9):3805–3810CrossRefPubMed Gao JK, Wang LX, Long B, Ye XT, Su JN, Yin XY, Zhou XX, Wang ZW (2015) Arsenic trioxide inhibits cell growth and invasion via Down- regulation of Skp2 in pancreatic Cancer cells. Asian Pac J Cancer Prev 16(9):3805–3810CrossRefPubMed
9.
go back to reference Li X, Ding X, Adrian TE (2003) Arsenic trioxide induces apoptosis in pancreatic cancer cells via changes in cell cycle, caspase activation, and GADD expression. Pancreas 27(2):174–179CrossRefPubMed Li X, Ding X, Adrian TE (2003) Arsenic trioxide induces apoptosis in pancreatic cancer cells via changes in cell cycle, caspase activation, and GADD expression. Pancreas 27(2):174–179CrossRefPubMed
12.
go back to reference Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43(Database issue):D447–D452. https://doi.org/10.1093/nar/gku1003 CrossRefPubMed Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43(Database issue):D447–D452. https://​doi.​org/​10.​1093/​nar/​gku1003 CrossRefPubMed
13.
go back to reference Ruan HH, Zhang Z, Wang SY, Nickels LM, Tian L, Qiao JJ, Zhu J (2017) Tumor necrosis factor receptor-associated factor 6 (TRAF6) mediates ubiquitination-dependent STAT3 activation upon Salmonella typhimurium infection. Infect Immun 85. https://doi.org/10.1128/iai.00081-17 Ruan HH, Zhang Z, Wang SY, Nickels LM, Tian L, Qiao JJ, Zhu J (2017) Tumor necrosis factor receptor-associated factor 6 (TRAF6) mediates ubiquitination-dependent STAT3 activation upon Salmonella typhimurium infection. Infect Immun 85. https://​doi.​org/​10.​1128/​iai.​00081-17
21.
26.
go back to reference Yurgelun MB, Masciari S, Joshi VA, Mercado RC, Lindor NM, Gallinger S, Hopper JL, Jenkins MA, Buchanan DD, Newcomb PA, Potter JD, Haile RW, Kucherlapati R, Syngal S, Colon Cancer Family Registry (2015) Germline TP53 mutations in patients with early-onset colorectal Cancer in the Colon Cancer family registry. JAMA Oncol 1(2):214–221. https://doi.org/10.1001/jamaoncol.2015.0197 CrossRefPubMed Yurgelun MB, Masciari S, Joshi VA, Mercado RC, Lindor NM, Gallinger S, Hopper JL, Jenkins MA, Buchanan DD, Newcomb PA, Potter JD, Haile RW, Kucherlapati R, Syngal S, Colon Cancer Family Registry (2015) Germline TP53 mutations in patients with early-onset colorectal Cancer in the Colon Cancer family registry. JAMA Oncol 1(2):214–221. https://​doi.​org/​10.​1001/​jamaoncol.​2015.​0197 CrossRefPubMed
32.
go back to reference Anvarian Z, Nojima H, van Kappel EC, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel RC, Kuper I, Richter K, Heck AJR, Boelens R, Vincent JP, Rüdiger SGD, Maurice MM (2016) Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network. Nat Struct Mol Biol 23(4):324–332. https://doi.org/10.1038/nsmb.3191 CrossRefPubMed Anvarian Z, Nojima H, van Kappel EC, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel RC, Kuper I, Richter K, Heck AJR, Boelens R, Vincent JP, Rüdiger SGD, Maurice MM (2016) Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network. Nat Struct Mol Biol 23(4):324–332. https://​doi.​org/​10.​1038/​nsmb.​3191 CrossRefPubMed
33.
go back to reference Wu R, Zhai Y, Fearon ER, Cho KR (2001) Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res 61(22):8247–8255PubMed Wu R, Zhai Y, Fearon ER, Cho KR (2001) Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res 61(22):8247–8255PubMed
34.
go back to reference Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z (1996) In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88(3):1052–1061PubMed Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z (1996) In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88(3):1052–1061PubMed
Metadata
Title
Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer
Authors
Yanan Pang
Zhiyong Liu
Shanrong Liu
Publication date
01-04-2019
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-018-0543-0

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