Gene Summary

Gene:PARK7; Parkinsonism associated deglycase
Aliases: DJ1, DJ-1, GATD2, HEL-S-67p
Summary:The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:protein/nucleic acid deglycase DJ-1
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (6)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: PARK7 (cancer-related)

Pan XK, Su F, Xu LH, et al.
DJ-1 Alters Epirubicin-induced Apoptosis via Modulating Epirubicinactivated Autophagy in Human Gastric Cancer Cells.
Curr Med Sci. 2018; 38(6):1018-1024 [PubMed] Related Publications
Epirubicin, which is a conventional chemotherapeutic drug for gastric cancer, has innate and adaptive chemoresistance. Recent studies revealed that epirubicin could induce autophagy as a defensive mechanism in drug resistance of mammary carcinoma. Another study implied that DJ-1 may be a chemoresistance-related gene. But the association between DJ-1 and drug resistance of epirubicin in gastric cancer is still ambiguous. In the present report, we explored whether and how DJ-1 conduced to epirubicin-induced apoptosis in gastric cancer. Epirubicin dose-dependently increased the expression of DJ-1 and induced autophagy. Knockdown of DJ-1 notably enhanced epirubicin-induced cell apoptosis, whereas overexpression of DJ-1 attenuated epirubicin-induced cell apoptosis. Further studies revealed that down-regulation of DJ-1 modulated epirubicinactivated autophagy which augmented epirubicin-induced apoptosis. In conclusion, our results validated that DJ-1 reduced epirubicin-induced apoptosis in gastric cancer cells via modulating epirubicin-activated autophagy.

Ernst EH, Lykke-Hartmann K
Transcripts encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles.
J Assist Reprod Genet. 2018; 35(10):1787-1798 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
PURPOSE: To study the presence and distribution of genes encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles.
METHODS: A class comparison study on existing granulosa cell transcriptome from primordial (n = 539 follicles) and primary (n = 261) follicles donated by three women having ovarian tissue cryopreserved before chemotherapy was performed and interrogated.
RESULTS: In granulosa cells from primordial follicles, 30 genes were annotated 'mitochondrial dysfunction' including transcripts (PRDX5, TXN2) encoding enzymatic free radical scavengers peroxiredoxin 5 and thioredoxin 2. Several apoptosis regulation genes were noted (BCL2, CAS8, CAS9, AIFM1). In granulosa cells from primary follicles, mitochondrial dysfunction signalling pathway was annotated. High expression of transcripts encoding the free radical scavenger peroxiredoxin 3, as well as anti-apoptotic enzyme BCL2, was found. Interestingly, PARK7 encoding the deglycase (DJ-1) protein was expressed in granulosa cells from primary follicles. DJ-1 is implicated in oxidative defence and functions as a positive regulator of the androgen receptor and as a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/serine-threonine protein kinase (AKT) signalling pathway suppressor PTEN.
CONCLUSIONS: The results indicate extensive energy production and free radical scavenging in the granulosa cells of primordial follicles with potential implications for ovarian ageing, cigarette smoking, premature ovarian failure and polycystic ovarian syndrome. Furthermore, DJ-1 may be involved in androgen responsiveness and the regulation of follicle growth via PI3K/PTEN/AKT signalling pathway regulation in the granulosa cells of primary follicles. The involvement of mitochondrial free radical production in the age-related decline of competent oocytes is becoming apparent.

Gladitz J, Klink B, Seifert M
Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion.
Acta Neuropathol Commun. 2018; 6(1):49 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Oligodendrogliomas are primary human brain tumors with a characteristic 1p/19q co-deletion of important prognostic relevance, but little is known about the pathology of this chromosomal mutation. We developed a network-based approach to identify novel cancer gene candidates in the region of the 1p/19q co-deletion. Gene regulatory networks were learned from gene expression and copy number data of 178 oligodendrogliomas and further used to quantify putative impacts of differentially expressed genes of the 1p/19q region on cancer-relevant pathways. We predicted 8 genes with strong impact on signaling pathways and 14 genes with strong impact on metabolic pathways widespread across the region of the 1p/19 co-deletion. Many of these candidates (e.g. ELTD1, SDHB, SEPW1, SLC17A7, SZRD1, THAP3, ZBTB17) are likely to push, whereas others (e.g. CAP1, HBXIP, KLK6, PARK7, PTAFR) might counteract oligodendroglioma development. For example, ELTD1, a functionally validated glioblastoma oncogene located on 1p, was overexpressed. Further, the known glioblastoma tumor suppressor SLC17A7 located on 19q was underexpressed. Moreover, known epigenetic alterations triggered by mutated SDHB in paragangliomas suggest that underexpressed SDHB in oligodendrogliomas may support and possibly enhance the epigenetic reprogramming induced by the IDH-mutation. We further analyzed rarely observed deletions and duplications of chromosomal arms within oligodendroglioma subcohorts identifying putative oncogenes and tumor suppressors that possibly influence the development of oligodendroglioma subgroups. Our in-depth computational study contributes to a better understanding of the pathology of the 1p/19q co-deletion and other chromosomal arm mutations. This might open opportunities for functional validations and new therapeutic strategies.

Yang TY, Wu YJ, Chang CI, et al.
The Effect of Bornyl
Int J Mol Sci. 2018; 19(5) [PubMed] Article available free on PMC after 01/10/2019 Related Publications

Vavougios G, Zarogiannis SG, Doskas T
The putative interplay between DJ-1/NRF2 and Dimethyl Fumarate: A potentially important pharmacological target.
Mult Scler Relat Disord. 2018; 21:88-91 [PubMed] Related Publications
Recent research has outlined that Dimethyl Fumarate (DMF) functions as a gene regulator via multiple pathways, critical among which is the NRF2 cytoprotective cascade. PARK7/DJ-1 is a multifunctional protein that acts as a redox sensor and effector of multiple cytoprotective pathways, including NRF2. Specifically, it prevents the association of NRF2 with its inhibitor KEAP1, allowing NRF2 to enter the nucleus and mediate cytoprotective and antioxidant cascades. It is our hypothesis that while the NRF2-KEAP1 inhibitory complex is reported the main pharmacological target for DMF's NRF dependent functions, no study to date has explored the effects of DMF on DJ-1's expression, and vice-versa, the possibility of a regulatory inadequacy in the upstream, oxidant-responsive DJ-1 activator of the NRF2 cascade.

Cao J, Chen X, Ying M, et al.
DJ-1 as a Therapeutic Target Against Cancer.
Adv Exp Med Biol. 2017; 1037:203-222 [PubMed] Related Publications
DJ-1 is a gene involved in various cellular processes, including transcriptional regulation, oxidative stress response, fertilization, mitochondrial regulation, inflammatory and fibrogenic niche formation, and glycation damage prevention. Although a disease-associated genetic study within the past decade has demonstrated that the mutation of DJ-1 is associated with autosomal early-onset Parkinson's disease, increasing evidence suggests that DJ-1 also plays a critical role in tumor development and progression. In this review, we provide an overview of current knowledge concerning the role and the mechanism of DJ-1 in cancer and also discuss the possibility of DJ-1 as a therapeutic target against cancer.

Oh SE, Mouradian MM
Regulation of Signal Transduction by DJ-1.
Adv Exp Med Biol. 2017; 1037:97-131 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. It attenuates cell death signaling by inhibiting apoptosis signal-regulating kinase 1 (ASK1) activation as well as by inhibiting mitogen-activated protein kinase kinase kinase 1 (MEKK1/MAP3K1) activation of downstream apoptotic cascades. It also modulates autophagy through the ERK, Akt, or the JNK/Beclin1 pathways. In addition, DJ-1 regulates the transcription of genes essential for male reproductive function, such as spermatogenesis, by relaying nuclear receptor androgen receptor (AR) signaling. In this chapter, we summarize the ways that DJ-1 regulates these pathways, focusing on how its role in signal transduction contributes to cellular homeostasis and the pathologic states that result from dysregulation.

Kawate T, Tsuchiya B, Iwaya K
Expression of DJ-1 in Cancer Cells: Its Correlation with Clinical Significance.
Adv Exp Med Biol. 2017; 1037:45-59 [PubMed] Related Publications
Upregulation of DJ-1 mRNA is commonly observed in various human cancers such as ductal carcinoma of the breast, non-small cell carcinoma of the lung, pancreatic duct adenocarcinoma, urinary transitional cell carcinoma, and gynecologic carcinoma. At the protein level, intensity and intracellular localization of DJ-1 expression is varied, and the DJ-1 protein regulates cancer progression, clinical aggressiveness, differentiation, cancer cell morphology, and drug sensitivity. Thus, DJ-1 plays a critical role in cancer. Although DJ-1 has an important role within cancer cells, cancer cells secrete DJ-1 outside the cells. DJ-1 may serve as a tumor marker that can be detected from an early stage in the blood, secretory fluids, ascites, or pleural effusion.

Ariga H, Iguchi-Ariga SMM
Adv Exp Med Biol. 2017; 1037:1-4 [PubMed] Related Publications
The DJ-1 gene is an oncogene and also causative gene for a familial form of Parkinson disease. Although exits of cancer and neurodegenerative diseases, including Parkinson disease, are completely opposite, there are some common points of view between both diseases, including growth and death signaling pathways, and oxidative stresses affect the onset and pathogenesis of both cancer and neurodegenerative diseases. DJ-1 has versatile functions and plays a role in protection against oxidative stress. Inactivation and/or excess activation of DJ-1 functions, therefore, leads to onsets of oxidative stress-related diseases such as type 2 diabetes and male infertility in addition to cancer and neurodegenerative diseases, and studies about DJ-1 will give rise to the common mechanism among these diseases. Furthermore, secreted DJ-1 levels in serum and DJ-1-binding compounds will be a diagnostic biomarker and therapeutic drug for neurodegenerative diseases, respectively.

Wang Y, Zhang Y, Lu Q, et al.
NRG-1 Stimulates Serum DJ-1 Increase in Breast Cancers.
Pathol Oncol Res. 2019; 25(1):71-79 [PubMed] Related Publications
To explore the relationship between the expression of DJ-1/HER3 and tumor grade in breast cancer, and investigate the effect of HER3 on NRG-1-mediated serum DJ-1 level in vivo. We analyze the expression level of DJ-1 and HER3 in 68 patients with different grades of breast cancer by immunostaining the tissue microarray. Besides, we investigated the serum DJ-1 level by ELISA. We found that the detectable DJ-1 protein expression is decreased, and the HER3 expression is increased in tumor tissue with the progression of breast cancer. There is a significant rise of DJ-1 in serum in vivo with the stimulation of NRG-1. Meanwhile, we found that HER3 knockdown abolishes NRG-1-induced serum DJ-1 increase and HER3 overexpress improves NRG-1-induced serum DJ-1 increase. This study provides a serum biomarker for breast cancer. The results showed that DJ-1 was associated with clinical stage of breast cancer, and NRG-1 increased the dissociation of HER3 and DJ-1, with promoting the level of DJ-1 in peripheral blood. It is suggested that the level of DJ-1 in peripheral blood may be conducive to assess the prognosis of patients with breast cancer and serum DJ-1 levels can serve as an indicator of therapeutic effectiveness for the development of HER3 targeting breast cancer antibody therapies.

Drapalo K, Jozwiak J
Parkin, PINK1 and DJ1 as possible modulators of mTOR pathway in ganglioglioma.
Int J Neurosci. 2018; 128(2):167-174 [PubMed] Related Publications
PURPOSE: Ganglioglioma (GG) is a non-malignant tumor classified as G1 by the WHO. Although we currently know that the neoplasm may result from the hyperactivity of protein kinase B (PKB or Akt) or extracellular-regulated kinase (Erk), which upregulates mammalian target of rapamycin kinase (mTOR) and leads to translation of proteins responsible for cell cycle regulation, there are still many questions to be answered. In the current paper we try to analyze the link between GG formation and activity of three proteins known to play a role in neuroprotection (parkin, PINK1 and DJ1).
MATERIALS AND METHODS: In our paper, we review the current information on the involvement of these proteins in the transmission of information in the cell and triggering various cell signals, like survival or apoptosis. We also review current literature data on involvement of parkin, DJ1 and PINK1 in the regulation of mTOR, the pathway probably contributing to the development of GG.
RESULTS: Parkin is an E3 ubiquitin ligase, shown to trigger proteasome-dependent degradation and autophagy, necessary for the maintenance of homeostasis in neurons. PINK1, a mitochondrial protein kinase, is required for mitochondrial maintenance and neuronal survival. DJ1 is a sensor of reactive oxygen species, and protects the cells against oxidative stress. Mutations in the genes encoding these three proteins are known to underlie autosomal recessive forms of Parkinson's disease, as well as other neurodegenerative and neuroinflammatory disorders.
CONCLUSION: It appears that mutations of parkin, PINK1 and DJ1 may result in the development of both neurodegeneration and tumors. Also, these proteins might be used as markers of disease, thus allowing better diagnosis and therapy.

Han B, Wang J, Gao J, et al.
DJ-1 as a potential biomarker for the early diagnosis in lung cancer patients.
Tumour Biol. 2017; 39(6):1010428317714625 [PubMed] Related Publications
DJ-1 is a novel oncogene that can transform NIH3T3 cells in cooperation with the activated ras gene. DJ-1 appears to have its greatest effect on tumourigenesis, and it may have a greater impact on early-stage lung cancers. In this study, we proposed to investigate the clinical value of DJ-1 protein in the early diagnosis of lung cancer and compared its diagnostic value with other biomarkers. Preoperative serum DJ-1 levels were measured in 300 lung cancer patients and compared with benign pulmonary disease (n = 44) and healthy volunteers (n = 64). Using tissue microarrays and immunohistochemical analyses, we compared the DJ-1 expression between the primary squamous cell carcinoma tumours and matched metastatic tissues from a lymph node. The baseline preoperative serum DJ-1 of lung cancer patients was significantly higher than that of benign diseases and healthy controls (p < 0.001). In the early-stage subgroup, the median DJ-1 concentration (ng/mL) was significantly higher than that of the advanced stage (12.90 vs 7.75, p < 0.05). Using immunohistochemistry, we observed that the DJ-1 staining intensity was generally weaker and less common in the metastatic tissues compared with that in the primary tumour (McNemar-Bowker Test, p = 0.008). DJ-1 was highly expressed in the early stage of lung cancer, and its expression was significantly decreased after metastasis. Therefore, DJ-1 may be a potential biomarker for the early diagnosis and monitoring of lung cancer metastasis.

Ling H, He J, Tan H, et al.
Identification of potential targets for differentiation in human leukemia cells induced by diallyl disulfide.
Int J Oncol. 2017; 50(2):697-707 [PubMed] Related Publications
Diallyl disulfide (DADS) is a primary component of garlic, which has chemopreventive potential. We previously found that moderate doses (15-120 µM) of DADS induced apoptosis and G2/M phase cell cycle arrest. In this study, we observed the effect of low doses (8 µM) of DADS on human leukemia HL-60 cells. We found that DADS could inhibit proliferation, migration and invasion in HL-60 cells, and arrested cells at G0/G1 stage. Then, cell differentiation was displayed by morphologic observation, NBT reduction activity and CD11b evaluation of cytometric flow. It showed that DADS induced differentiation, reduced the ability of NBT and increased CD11b expression. Likewise, DADS inhibited xenograft tumor growth and induced differentiation in vivo. In order to make sure how DADS induced differentiation, we compared the protein expression profile of DADS-treated cells with that of untreated control. Using high resolution mass spectrometry, we identified 18 differentially expressed proteins after treatment with DADS, including four upregulated and 14 downregulated proteins. RT-PCR and western blot assay showed that DJ-1, cofilin 1, RhoGDP dissociation inhibitor 2 (RhoGDI2), Calreticulin (CTR) and PCNA were decreased by DADS. These data suggest that the effects of DADS on leukemia may be due to multiple targets for intervention.

Saidu NE, Noé G, Cerles O, et al.
Dimethyl Fumarate Controls the NRF2/DJ-1 Axis in Cancer Cells: Therapeutic Applications.
Mol Cancer Ther. 2017; 16(3):529-539 [PubMed] Related Publications
The transcription factor NRF2 (NFE2L2), regulates important antioxidant and cytoprotective genes. It enhances cancer cell proliferation and promotes chemoresistance in several cancers. Dimethyl fumarate (DMF) is known to promote NRF2 activity in noncancer models. We combined

Raninga PV, Di Trapani G, Vuckovic S, Tonissen KF
Targeted knockdown of DJ-1 induces multiple myeloma cell death via KLF6 upregulation.
Apoptosis. 2016; 21(12):1422-1437 [PubMed] Related Publications
Multiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson's disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shorter overall survival and poor prognosis in MM patients. Targeted DJ-1 knockdown using siRNAs induced necroptosis in myeloma cells. We found that Krüppel-like factor 6 (KLF6) is expressed at lower levels in myeloma cells compared to PBMCs, and DJ-1 knockdown increased KLF6 expression in myeloma cells. Targeted knockdown of KLF6 expression in DJ-1 knockdown myeloma cells rescued these cells from undergoing cell death. Higher DJ-1 levels were observed in bortezomib-resistant myeloma cells compared to parent cells, and siRNA-mediated DJ-1 knockdown reversed bortezomib resistance. DJ-1 knockdown increased KLF6 expression in bortezomib-resistant myeloma cells, and subsequent siRNA-mediated KLF6 knockdown rescued bortezomib-resistant myeloma cells from undergoing cell death. We also demonstrated that specific siRNA-mediated DJ-1 knockdown reduced myeloma cell growth under a hypoxic microenvironment. DJ-1 knockdown reduced the expression of HIF-1α and its target genes in hypoxic-myeloma cells, and overcame hypoxia-induced bortezomib resistance. Our findings demonstrate that elevated DJ-1 levels correlate with myeloma cell survival and acquisition of bortezomib resistance. Thus, we propose that inhibiting DJ-1 may be an effective therapeutic strategy to treat newly diagnosed as well as relapsed/refractory MM patients.

Li Q, Tang Y, Qin J, et al.
Subcellular localization of DJ-1 in human HL-60 leukemia cells in response to diallyl disulfide treatment.
Mol Med Rep. 2016; 14(5):4666-4672 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Diallyl disulfide (DADS) has been demonstrated to exert potent anticancer effects in vitro and in vivo. Previous studies indicate that DADS may induce the differentiation and/or apoptosis of human leukemia cells in vitro. However, the mechanisms underlying these anticancer effects remain elusive. The aim of the present study was to investigate alterations in the subcellular localization of protein deglycase DJ‑1 (also known as Parkinsonism associated deglycase-7, PARK-7) in the cytoplasm, nucleus and mitochondria of human leukemia HL‑60 cells induced by DADS, in order to provide novel experimental evidence for the molecular mechanisms underlying the anticancer mechanisms of DADS in leukemia cells. HL‑60 cells induced by DADS were collected at different time points, and proteins from the cytoplasm, nucleus and mitochondria of the cells were isolated using specific cellular component isolation kits. The protein expression levels of DJ‑1 in these subcellular fractions of HL60 cells following exposure to DADS for varying lengths of time, were determined using western blotting, immunocytochemistry and immunofluorescence techniques. Following exposure of HL‑60 cells to 1.25 mg/l DADS for 8 h, the protein expression levels of DJ‑1 were significantly decreased in the cytoplasm, while nuclear fractions exhibited a significant increase in DJ‑1 expression when compared with untreated controls. The protein expression levels of DJ‑1 in mitochondria of HL‑60 cells were significantly decreased following treatment with 5 and 10 mg/l DADS. These results demonstrate that exposure of HL‑60 cells to low concentrations of DADS may promote DJ‑1 protein translocation from the cytoplasm to the nucleus, which suggests that DJ‑1 may function as a transcription factor or cofactor binding protein in the process of cell differentiation. The expression of DJ‑1 in mitochondria may be associated with induction of apoptosis in HL‑60 cells treated with moderate doses of DADS.

Sen NE, Drost J, Gispert S, et al.
Search for SCA2 blood RNA biomarkers highlights Ataxin-2 as strong modifier of the mitochondrial factor PINK1 levels.
Neurobiol Dis. 2016; 96:115-126 [PubMed] Related Publications
Ataxin-2 (ATXN2) polyglutamine domain expansions of large size result in an autosomal dominantly inherited multi-system-atrophy of the nervous system named spinocerebellar ataxia type 2 (SCA2), while expansions of intermediate size act as polygenic risk factors for motor neuron disease (ALS and FTLD) and perhaps also for Levodopa-responsive Parkinson's disease (PD). In view of the established role of ATXN2 for RNA processing in periods of cell stress and the expression of ATXN2 in blood cells such as platelets, we investigated whether global deep RNA sequencing of whole blood from SCA2 patients identifies a molecular profile which might serve as diagnostic biomarker. The bioinformatic analysis of SCA2 blood global transcriptomics revealed various significant effects on RNA processing pathways, as well as the pathways of Huntington's disease and PD where mitochondrial dysfunction is crucial. Notably, an induction of PINK1 and PARK7 expression was observed. Conversely, expression of Pink1 was severely decreased upon global transcriptome profiling of Atxn2-knockout mouse cerebellum and liver, in parallel to strong effects on Opa1 and Ghitm, which encode known mitochondrial dynamics regulators. These results were validated by quantitative PCR and immunoblots. Starvation stress of human SH-SY5Y neuroblastoma cells led to a transcriptional phasic induction of ATXN2 in parallel to PINK1, and the knockdown of one enhanced the expression of the other during stress response. These findings suggest that ATXN2 may modify the known PINK1 roles for mitochondrial quality control and autophagy during cell stress. Given that PINK1 is responsible for autosomal recessive juvenile PD, this genetic interaction provides a concept how the degeneration of nigrostriatal dopaminergic neurons and the Parkinson phenotype may be triggered by ATXN2 mutations.

Wang H, Gao W
DJ-1 Expression in Cervical Carcinoma and its Effects on Cell Viability and Apoptosis.
Med Sci Monit. 2016; 22:2943-9 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND This study aimed to investigate the expression of DJ-1 in cervical carcinoma and its effects on cell viability and apoptosis. MATERIAL AND METHODS Cervical carcinoma cell line Hela and 85 tissue samples, including 45 primary tumor biopsies, 30 para-carcinoma tissues, and 10 normal cervical tissues samples were used in this study. The expressions of DJ-1 in cervical carcinoma tissue, para-carcinoma tissue, and normal tissue samples were investigated by immunohistochemistry. DJ-1 expression in Hela cells was also investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. DJ-1 was interfered and transfected with siRNA, then cell viability and apoptosis were assayed by MTT and flow cytometry, respectively. Additionally, the expressions of phosphatase and tensin homolog (PTEN), AKT, and phospho-AKT (P-AKT) were detected. RESULTS Immunohistochemistry results showed that DJ-1 was highly expressed in cervical carcinoma tissues. In Hela cells, the expression of DJ-1 was significantly higher than that in normal controls (P<0.05). When cells were treated with DJ-1 siRNA, the cell viability decreased significantly (P<0.05), and the percentage of apoptosis cells increased significantly (P<0.05). In addition, the expressions of PTEN and AKT were significantly higher in the DJ-1 siRNA treatment group than those in the control group (P<0.05). The expression of p-AKT was significantly lower in the DJ-1 siRNA treatment group than in the control group and the DJ-1 over-expression group (P<0.05). CONCLUSIONS The aberrant up-regulation of DJ-1 expression might be an important step in the pathogenesis of cervical carcinoma.

Chai Y, Wang G, Fan L, Zhao M
A proteomic analysis of mushroom polysaccharide-treated HepG2 cells.
Sci Rep. 2016; 6:23565 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The anti-tumor properties of fungal polysaccharides have gained significant recognition in Asia and tropical America. In this study, the differential expression of proteins in normal HepG2 cells and those treated with polysaccharides that had been isolated from Phellinus linteus (PL), Ganoderma lucidum (GL) and Auricularia auricula (AA) was investigated. Using two-dimensional electrophoresis (2DE), a total of 104 protein spots were determined to be overexpressed in these cells compared with noncancerous regions. A total of 59 differentially expressed proteins were identified through MALDI-TOF-MS. In addition, 400 biological processes (BP), 133 cell components (CC) and 146 molecular functions (MF) were enriched by Gene Ontology (GO) analysis, and 78 KEGG pathways were enriched by pathway enrichment. Protein-Protein Interaction (PPI) analysis demonstrated the interaction networks affected by polysaccharides in HepG2 cells. Then, DJ-1 and 14-3-3 were identified as the key proteins in the networks, and the expression of the mRNA and proteins were evaluated using Real-time quantitative PCR (qRT-PCR) and Western blotting (WB), respectively. The results were in agreement with the 2DE. These results provided information on significant proteins of hepatocellular carcinoma (HCC) and form an important basis for the future development of valuable medicinal mushroom resources.

Zhang GQ, He C, Tao L, Liu F
Role of DJ-1 siRNA in reverse sensitivity of breast cancer cells to chemotherapy and its possible mechanism.
Int J Clin Exp Pathol. 2015; 8(6):6944-51 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Breast cancer which has a high incidence rate is the 2(nd) lethal diseases only followed by lung cancer in women. How to improve the recovery rate is the principal problem should be solved in clinical. Previous studies demonstrated the importance of DJ-1 in the existence of breast cancer for the secreted of protein into serum by breast cancer cells both in vitro and in vivo. So the DJ-1 probably could be selected as the target in breast cancer treatment. Adriamycin resistance breast cancer cells MCF-7 and DJ-1 siRNA plasmid were employed to explore the potential clinical application of DJ-1 in this study. Our results showed that the sensitivity of cancer cells to chemotherapeutics was significantly improved with the transfection of DJ-1 siRNA. Further mechanism studies indicated the role of PI3K/AKT/MTOR pathway in the improvement of apoptosis after treatment with adriamycin in DJ-1 silence group.

Vavougios GD, Solenov EI, Hatzoglou C, et al.
Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma.
Am J Physiol Lung Cell Mol Physiol. 2015; 309(7):L677-86 [PubMed] Related Publications
The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified. In the Gordon Mesothelioma Study, 34 of them were assessed out of which SUMO1, UBC3, KIAA0101, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7, HTRA2, and STUB1 were significantly overexpressed whereas TRAF6 and MTA2 were significantly underexpressed in MPM patients (network 2). Furthermore, Kaplan-Meier analysis revealed that MPM patients with high BBS1 expression had a median overall survival of 16.5 vs. 8.7 mo of those that had low expression. For validation purposes, we performed a meta-analysis in Oncomine database in five sarcoma datasets. Eight network 2 genes (KIAA0101, HDAC2, SUMO1, RBBP4, NONO, RBBP7, HTRA2, and MTA2) were significantly differentially expressed in an array of 18 different sarcoma types. Finally, Gene Ontology annotation enrichment analysis revealed significant roles of the PARK7 interactome in NuRD, CHD, and SWI/SNF protein complexes. In conclusion, we identified 13 novel genes differentially expressed in MPM, never reported before. Among them, BBS1 emerged as a novel predictor of overall survival in MPM. Finally, we identified that PARK7 interactome is involved in novel pathways pertinent in MPM disease.

Liu QX, Zheng H, Deng XF, et al.
Status of the Parkinson's disease gene family expression in non-small-cell lung cancer.
World J Surg Oncol. 2015; 13:238 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND: The purpose of this study is to detect the Parkinson's disease gene family mRNA relative expression in the non-small-cell lung cancer (NSCLC) tumor tissue and analyze the association between tumor characteristics and the Parkinson's disease gene family.
METHODS: Tumor tissue and tumor-adjacent tissue of 114 NSCLC patients were collected and SYBR quantitative analysis was used to detect the relative expression level of nine Parkinson's disease gene mRNAs. Then, paired sample test, two-sided Student's t-test, or two-sided Wilcoxon rank sum test was performed to analyze the mRNA relative expression level of nine Parkinson's disease gene mRNAs in different gender, tumor histology, and tumor stage.
RESULTS: Overexpression in the tumors was detected in 46/114 (40.35%) PARK1/4, 74/114 (64.91%) PARK2, 104/114 (91.23%) PARK5, 95/114 (83.33%) PARK6, 80/114 (70.18%) PARK7, 55/114 (48.25%) PARK8, 100/114 (87.72%) PARK9, 55/114 (48.25%) PARK15, and 99/114 (86.84%) glucocerebrosidase (GBA). Five genes PARK5 (91.23%), PARK6 (83.33%), PARK7 (70.18%), PARK9 (87.72%), and GBA (86.84%) were supposed to be overexpressed in the lung tumor tissues compared with tumor-adjacent tissues. There was no significant difference in PARK1/4, PARK2, PARK5, PARK9, and GBA mRNA expression by different tumor stage, whereas, PARK6, PARK7, PARK8, and PARK15 mRNA expression were found to have significant difference in the comparison of different tumor stages. The expression of PARK6 (P=0.01, P=0.03) and PARK15 (P<0.001, P<0.001) were significantly higher in stages I and II when compared with stage III, respectively. NSCLC patients in stage I showed the higher expression PARK7 compared to the patients in stage II (P=0.003).
CONCLUSIONS: The high expression of PARK6, PARK7, and PARK15 might lead to the occurrence of a primary NSCLC tumor, and the tumor with a decreasing expression of these three genes tends to be stages II and III. The results of our study indicate that the Parkinson's disease gene family may be a potential marker for the prediction of NSCLC.

Schumann C, Taratula O, Khalimonchuk O, et al.
ROS-induced nanotherapeutic approach for ovarian cancer treatment based on the combinatorial effect of photodynamic therapy and DJ-1 gene suppression.
Nanomedicine. 2015; 11(8):1961-70 [PubMed] Related Publications
UNLABELLED: This study represents a novel approach for intraoperative ovarian cancer treatment based on the combinatorial effect of a targeted photodynamic therapy (PDT) associated with suppression of the DJ-1 protein, one of the key players in the ROS defense of cancer cells. To assess the potential of the developed therapy, dendrimer-based nanoplatforms for cancer-targeted delivery of near-infrared photosensitizer, phthalocyanine, and DJ-1 siRNA have been constructed. In vitro studies revealed that therapeutic efficacy of the combinatorial approach was enhanced when compared to PDT alone and this enhancement was more pronounced in ovarian carcinoma cells, which are characterized by higher basal levels of DJ-1 protein. Moreover, the ovarian cancer tumors exposed to a single dose of combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence. Thus, the developed therapeutic approach can be potentially employed intraoperatively to eradicate unresactable cancer cells.
FROM THE CLINICAL EDITOR: The complete clearance of microscopic residual tumor cells during excision surgery is important to improve survival of the patient. In this interesting paper, the authors developed a novel approach using targeted photodynamic therapy (PDT), combining a photosensitizer, phthalocyanine, and DJ-1 siRNA for the treatment of ovarian cancer. The data showed that this approach increased cancer cell killing and may pave way for future clinical studies.

Ariga H
Common mechanisms of onset of cancer and neurodegenerative diseases.
Biol Pharm Bull. 2015; 38(6):795-808 [PubMed] Related Publications
Onset of cancer and neurodegenerative disease occurs by abnormal cell growth and neuronal cell death, respectively, and the number of patients with both diseases has been increasing in parallel with an increase in mean lifetime, especially in developed countries. Although both diseases are sporadic, about 10% of the diseases are genetically inherited, and analyses of such familial forms of gene products have contributed to an understanding of the molecular mechanisms underlying the onset and pathogenesis of these diseases. I have been working on c-myc, a protooncogene, for a long time and identified various c-Myc-binding proteins that play roles in c-Myc-derived tumorigenesis. Among these proteins, some proteins have been found to be also responsible for the onset of neurodegenerative diseases, including Parkinson's disease, retinitis pigmentosa and cerebellar atrophy. In this review, I summarize our findings indicating the common mechanisms of onset between cancer and neurodegenerative diseases, with a focus on genes such as DJ-1 and Myc-Modulator 1 (MM-1) and signaling pathways that contribute to the onset and pathogenesis of cancer and neurodegenerative diseases.

Zhu XL, Sun W, Lei WB, et al.
DJ-1-induced phosphatase and tensin homologue downregulation is associated with proliferative and invasive activity of laryngeal cancer cells.
Mol Med Rep. 2015; 12(2):2003-8 [PubMed] Related Publications
DJ-1, a novel mitogen-dependent oncogene, has an important role in the progression of human malignancies, whereas tumor suppressor phosphatase and tensin homolog (PTEN) is known to control a variety of processes associated with cell survival, proliferation and invasion. DJ-1 overexpression was reported to be negatively correlated with PTEN expression in tumor tissues of patients with laryngeal squamous cell carcinoma (LSCC). In the present study, the effect of DJ-1 on PTEN in laryngeal cancer cells was investigated by transfecting DJ-1-specific small interfering (si)RNA into Hep-2 and SNU-899 cells. Cell survival and cell proliferative and invasive capacity were then evaluated. The results showed that siRNA targeting of DJ-1 effectively upregulated PTEN expression, resulting in enhanced cell death as well as decreased proliferation and invasion of Hep-2 and SNU-899 cells. The results of the present study indicated, for the first time, to the best of our knowledge, that DJ-1-induced PTEN downregulation is associated with proliferative and invasive activity of laryngeal cancer cells. The DJ-1 gene may have an important role in the tumorigenesis of LSCC.

Kawate T, Iwaya K, Koshikawa K, et al.
High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients.
Cancer Sci. 2015; 106(7):938-43 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
In patients with cancer and Parkinson's disease, the DJ-1 protein may be secreted into the serum during the impaired response of the underlying cell-protective mechanisms. In order to determine the clinical significance of DJ-1 protein in the sera of breast cancer patients, we examined blood samples from a breast cancer group (n = 180) and a non-cancerous control group (n = 300). Higher levels of DJ-1 were detected in the breast cancer group (mean level, 42.7 ng/mL) than the control group (28.3 ng/mL) by ELISA (P = 0.019). Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA. DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis. The isoform at the pI of 6.3 showed the highest intensity in all 11 cancer cases. Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025). These data indicate that high levels of DJ-1, probably of isoform at pI 6.3, is a candidate serum marker of breast cancer.

Ismail IA, Abdel Shakor AB, Hong SH
DJ-1 Protects Breast Cancer Cells Against 2'-Benzoyloxycinnamaldehyde-induced Oxidative Stress Independent of Nrf2.
J Cell Physiol. 2015; 230(9):2262-9 [PubMed] Related Publications
2'-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent. BCA effectively inhibited proliferation of MDA-MB-435 more than in MCF-7 breast cancer cells. Our recent findings showed that DJ-1 protects MCF7 cells from BCA-induced oxidative stress via its mitochondrial translocation and inhibition of the mitochondrial perturbation (Ismail et al., 2012). In this study, we addressed the question of whether Nrf2 works downstream to DJ-1 in mediating differential antiproliferation effects in MCF-7 and MDAMB-435 breast cancer cells induced by BCA treatment. BCA upregulated the expression and induced nuclear translocalization of DJ-1 and Nrf2 in only MCF-7 cells. However, in MDA-MB-435, BCA increased only Nrf2 expression without inducing DJ-1 and/or Nrf2 protein translocalization to the nucleus. Furthermore, DJ-1 knockdown decreased DJ-1 expression in both cells without affecting Nrf2 and its downstream target γ-GCS, suggesting that DJ-1-induced cell protection and works independent of Nrf2 signaling pathway.

Cao J, Lou S, Ying M, Yang B
DJ-1 as a human oncogene and potential therapeutic target.
Biochem Pharmacol. 2015; 93(3):241-50 [PubMed] Related Publications
DJ-1 is a cancer- and Parkinson's disease-associated protein that participates in different intracellular signaling pathways to protect cells from toxic stresses. DJ-1 expression, oxidation, localization, and phosphorylation are often altered in human tumors, and DJ-1 has been implicated in various aspects of transformation, including uncontrolled proliferation, invasion, metastasis, and resistance to chemotherapy and apoptosis. Despite the strong relationship between DJ-1 and cancer, which made it a particularly attractive therapeutic target for cancer treatment, the detailed mechanisms of how this oncogene coordinates altered signaling with cell survival remains elusive. In this commentary, we discuss the role of DJ-1 in transformation, highlight some of the significant aspects of and prospects for therapeutically targeting the DJ-1 signaling in cancer, and describe what the future may hold.

Liu S, Long G, Wei H, et al.
DJ-1 knockdown inhibits growth and xenograft‑induced tumor generation of human hepatocellular carcinoma cells.
Oncol Rep. 2015; 33(1):201-6 [PubMed] Related Publications
The aim of this study was to identify potential downstream effectors of the oncogene DJ-1 in hepatocellular carcinoma (HCC) cell lines, and examine its role in the Akt signaling pathway and HCC oncogenesis. Expression of the DJ-1 protein was assessed by immunoblotting in several human HCC cell lines. Knockdown of DJ-1 was achieved by transfecting DJ-1-specific short hairpin RNAs into the HepG2 HCC cell line. The effect of DJ-1 downregulation on phosphatase and tensin homolog (PTEN) and phosphorylated Akt was evaluated. In addition, cell cycle, proliferation, adhesion and invasion were analyzed in the DJ-1 knockdown of HepG2 cells. The growth of HepG2‑induced tumor was evaluated in a nude mouse model after DJ-1 silencing. Stable DJ-1 knockdown was achieved in HepG2 cells using a shRNA eukaryotic expression vector. Downregulation of DJ-1 increased PTEN expression but decreased phosphorylation of Akt in HepG2 cells. In addition, DJ-1 knockdown resulted in the decreased proliferation, adhesion and invasion of HepG2 cells in vitro, and inhibited the growth of HepG2-induced tumor in vivo. DJ-1 knockdown altered the malignant behavior of HepG2 cells, potentially through the Akt signaling pathway, suggesting a crucial role for DJ-1 in the oncogenesis of HCC.

Wang B, Qin H, Wang Y, et al.
Effect of DJ-1 overexpression on the proliferation, apoptosis, invasion and migration of laryngeal squamous cell carcinoma SNU-46 cells through PI3K/AKT/mTOR.
Oncol Rep. 2014; 32(3):1108-16 [PubMed] Related Publications
The aim of the present study was to explore the effect of DJ-1-mediated PI3K/AKT/mTOR pathway on the proliferation, apoptosis, invasion, migration and other tumor biological characteristics of laryngeal squamous cell SNU-46, through stable transfection and overexpression of the DJ-1 gene. Retrovirus carrying DJ-1 gene was used to stabilize transfected human laryngeal squamous carcinoma SNU-46 cell line, and monoclonal cell line of stably overexpressed DJ-1 protein was screened out by G418. DJ-1 protein expression was determined by western blotting, and changes of p-AKT, p-mTOR and PTEN protein content were detected, followed by the detection of changes in proliferation, apoptosis, invasion, migration and other tumor biological characteristics of laryngeal squamous carcinoma cell line with stably transfected DJ-1 protein overexpression by flow cytometry, CCK-8 method and Transwell. We successfully constructed a laryngeal squamous carcinoma cell line of stably overexpressed DJ-1 protein and termed it SNU-46-DJ-1. After overexpression of DJ-1 protein, the levels of PTEN expression in laryngeal squamous cell SNU-46 decreased and p-AKT and p-mTOR protein expression levels increased. Compared to the untreated SNU-46 cells, the proliferation rate of SNU-46-DJ-1 cells increased (0.834±0.336 vs. 0.676±0.112; p<0.001); invasiveness was enhanced (165.7±13.6 vs. 100.0±17.4; p=0.001), the migration ability was enhanced (207.3±13.1 vs. 175.3±13.3; p=0.036), and the apoptosis rate decreased (3.533±5.167 vs. 16.397±5.447%; p=0.019). The overexpression of DJ-1 protein in laryngeal squamous carcinoma SNU-46 cells can accelerate proliferation rate, increase the invasion and migration capacity, and reduce apoptosis, by activating the PI3K/AKT/mTOR pathway.

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