Disruption of a regulatory loop between DUSP1 and p53 contributes to hepatocellular carcinoma development and progression

Hao, Peipei; Li, Hua; Lee, Mi-Jin; Wang, Yunpeng; Kim, Jong-Hyun; Yu, Goung-Ran; Lee, Sangyeop; Leem, Sun‐Hee; Jang, Kyu-Yun; Kim, Dae‐Ghon

doi:10.1016/j.jhep.2014.12.033

Cited by 40 publications

(29 citation statements)

References 40 publications

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“…A South Korean study revealed that DUSP1 functioned as a tumor suppressor during hepatocarcinogenesis, and that the DUSP1 expression was associated with the activation of p53 (43). Hao et al (44) revealed that disruption of a positive regulatory loop between DUSP1 and p53 promoted HCC development and progression. Wei et al (45) found that miR-101 inhibited macrophage-induced growth of HCC tumors by regulating tumor growth factor-β secretion via targeting DUSP1.…”

Section: Discussionmentioning

confidence: 99%

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

2018

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The aim of the present study was to identify potential biomarkers of hepatocellular carcinoma (HCC). Three gene expression profiles of GSE95698, GSE49515 and GSE76427 and a DNA methylation profile of GSE73003 were downloaded from the Gene Expression Omnibus (GEO) database, each comprising data regarding HCC and control tissue samples. The differentially expressed genes (DEGs) between the HCC group and the control group were identified using the limma software package. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the overlapping DEGs. The PPI network of the overlapping DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins. A total of 41 DEGs were identified in HCC the group compared with control group. The overlapping DEGs were enriched in 11 GO terms and 3 KEGG pathways. A total of 6,349 DMSs were identified, and 6 of the differentially expressed genes were also differentially methylated [Denticleless protein homolog (), Dual specificity phosphatase 1 (), Eomesodermin, Endothelial cell specific molecule 1, Nuclear factor κ-light-chain gene enhancer of activated B cells inhibitor, α (NFKBIA) and suppressor of cytokine signaling 2 ()]. The present study suggested that and may be potential biomarkers of HCC, and the tumor protein 'p53 signaling', 'forkhead box O1' signaling and 'metabolic' pathways may serve roles in the pathogenesis of HCC.

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Section: Discussionmentioning

confidence: 99%

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

2018

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“…Human tumor cell lines SAOS, H1299, PC3, HT29, DLD-1, SW480, COLO205, and A293 cells were from the American Tissue Culture Collection (Rockville, MD). HLK3 cells were established and maintained in our laboratory 18 . Cells were cultured in DMEM medium (Sigma, St. Louis, MO) supplemented with 10% fetal bovine serum (Invitrogen, Carlsbad, CA), 1% penicillin and streptomycin solution (Sigma), 3 mM taurine, and 25 mM HEPES (Invitrogen) in air containing 5% CO 2 in an incubator, as previously described 18 .…”

Section: Methodsmentioning

confidence: 99%

“…HLK3 cells were established and maintained in our laboratory 18 . Cells were cultured in DMEM medium (Sigma, St. Louis, MO) supplemented with 10% fetal bovine serum (Invitrogen, Carlsbad, CA), 1% penicillin and streptomycin solution (Sigma), 3 mM taurine, and 25 mM HEPES (Invitrogen) in air containing 5% CO 2 in an incubator, as previously described 18 . HCT116 with p53 wild type and HCT116 that are p53 null were gifts from Dr. Bert Vogelstein (Johns Hopkins University, Baltimore, MD).…”

Section: Methodsmentioning

confidence: 99%

Alterations in the p53-SOCS2 axis contribute to tumor growth in colon cancer

Kim

Lee

et al. 2018

Exp Mol Med

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Altered expression of suppressor of cytokine signaling (SOCS) is found in various tumors. However, regulation of SOCS2 by upstream molecules has yet to be clearly elucidated, particularly in tumor cells. SCOCS2 expression was examined in tumor cells transfected with an inducible p53 expression system. The impact of SOCS2 on cell proliferation was measured with in vitro assays. Inhibition of tumorigenicity by SOCS2 knockdown was assessed via a mouse model. Expression profiles were compared and genes differentially expressed were identified using four types of p53-null cells (Saos, HLK3, PC3, and H1299) and the same cells stably expressing p53. Twelve kinds of target genes were simultaneously upregulated or downregulated by p53 in three or more sets of p53-null cells. SOCS2 expression was reciprocally inhibited by inducible p53 expression in p53-null cells, even colon cancer cells. SOCS2 promoter activity was inhibited by wild type but not mutant p53. SOCS2 knockdown inhibited tumor growth in vitro and in an animal xenograph model. SOCS2 overexpression was detected in a murine model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer compared to mock-treated controls. SOCS2 expression was heterogeneously upregulated in some human colon cancers. Thus, SOCS2 was upregulated by p53 dysfunction and seemed to be associated with the tumorigenic potential of colon cancer.

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“…Downregulating DUSP1 allows for proliferation and increased tumor mass in the more advanced stages of tumorigenesis by enhancing ERK/MAPK signaling pathway. DUSP1 expression was also found to be significantly lower in HCC patients with poor prognosis than the patients with better prognosis [36,37]. However, Calvisi [36] found DUSP1 was not the main causative event responsible for phosphorylated ERK (p-ERK) up-regulation in human HCC.…”

Section: Role Of Dusp1 In Tumor Progressionmentioning

confidence: 99%

“…Another study [39] indicated that p53 protein, as a tumor suppressor, suppresses cell growth by inducing cell cycle arrest or apoptosis via DUSP1. Recent study in HCC [37] revealed that wild-type p53 could directly bind to DUSP1 gene and transcriptionally upregulated DUSP1. DUSP1 was involved in p53 activation via the p38 MAPK/HSP27 pathway.…”

Section: Role Of Dusp1 In Tumor Progressionmentioning

confidence: 99%

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

et al. 2016

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Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threoninetyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signalregulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment. Cancer Medicine Open Access 2062

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Disruption of a regulatory loop between DUSP1 and p53 contributes to hepatocellular carcinoma development and progression

Cited by 40 publications

References 40 publications

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

Alterations in the p53-SOCS2 axis contribute to tumor growth in colon cancer

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

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