Peroxiredoxin I to VI (PRX I–VI), a family of highly conserved antioxidants, has been implicated in numerous diseases. There have been reports that PRXs are expressed aberrantly in a variety of tumors, implying that they could play an important role in carcinogenesis. Epigenetic mechanisms such as DNA methylation, histone modifications, and microRNAs have been reported to modulate expression of PRXs. In addition, the use of epigenetic regulators, such as histone deacetylases, has been demonstrated to restore PRX to normal levels, indicating that the reversible nature of epigenetics can be exploited for future treatments.
RheeSGKangSWChangTSJeongWJKimKH. Peroxiredoxin, a novel family of peroxidases. IUBMB Life2001; 52: 35–41.
2.
RheeSGChaeHZKimK. Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med2005; 38: 1543–52.
3.
WoodZASchroderERobin HarrisJPooleLB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci2003; 28: 32–40.
4.
RheeSGWooHAKilISBaeSH. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J Biol Chem2012; 287: 4403–10.
5.
ChangTSChoCSParkSYuSKangSWRheeSG. Peroxiredoxin III, a mitochondrion-specific peroxidase, regulates apoptotic signaling by mitochondria. J Biol Chem2004; 279: 41975–84.
6.
FujiiJIkedaYKurahashiTHommaT. Physiological and pathological views of peroxiredoxin 4. Free Radic Biol Med2015; 83: 373–9.
7.
AnBCLeeSSJungHSKimJYLeeYLeeKWLeeSYTripathiBNChungBY. An additional cysteine in a typical 2-Cys peroxiredoxin of pseudomonas promotes functional switching between peroxidase and molecular chaperone. FEBS Lett2015; 589: 2831–40.
8.
ChangTSJeongWWooHALeeSMParkSRheeSG. Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine. J Biol Chem2004; 279: 50994–1001.
9.
WooHAChaeHZHwangSCYangKSKangSWKimKRheeSG. Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic acid formation. Science (New York, NY)2003; 300: 653–6.
10.
SorianoFXPapadiaSBellKFHardinghamGE. Role of histone acetylation in the activity-dependent regulation of sulfiredoxin and sestrin 2. Epigenetics2009; 4: 152–8.
11.
RheeSGWooHA. Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H2O2, and protein chaperones. Antioxid Redox Signal2011; 15: 781–94.
12.
ConwayMELeeC. The redox switch that regulates molecular chaperones. Biomol Concepts2015; 6: 269–84.
13.
WoodZAPooleLBKarplusPA. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science (New York, NY)2003; 300: 650–3.
14.
KrapfenbauerKEngidaworkECairnsNFountoulakisMLubecG. Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders. Brain Res2003; 967: 152–60.
15.
YunHMChoiDYOhKWHongJT. PRDX6 exacerbates dopaminergic neurodegeneration in a MPTP mouse model of Parkinson’s disease. Mol Neurobiol2015; 52: 422–31.
KarihtalaPMantyniemiAKangSWKinnulaVLSoiniY. Peroxiredoxins in breast carcinoma. Clin Cancer Res2003; 9: 3418–24.
18.
HanahanDWeinberg RobertA. Hallmarks of cancer: the next generation. Cell2011; 144: 646–74.
19.
VerbonEHPostJABoonstraJ. The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene2012; 511: 1–6.
20.
BoonstraJPostJA. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene2004; 337: 1–13.
21.
InoguchiTSontaTTsubouchiHEtohTKakimotoMSonodaNSatoNSekiguchiNKobayashiKSumimotoHUtsumiHNawataH. Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NADPH oxidase. J Am Soc Nephrol2003; 14: S227–32.
22.
ChuaPJLeeEHYuYYipGWTanPHBayBH. Silencing the peroxiredoxin III gene inhibits cell proliferation in breast cancer. Int J Oncol2010; 36: 359–64.
23.
LuWFuZWangHFengJWeiJGuoJ. Peroxiredoxin 2 knockdown by RNA interference inhibits the growth of colorectal cancer cells by downregulating Wnt/β-catenin signaling. Cancer Lett2014; 343: 190–9.
24.
ChangXZLiDQHouYFWuJLuJSDiGHJinWOuZLShenZZShaoZM. Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer. Breast Cancer Res2007; 9: R76–R76.
25.
LeeSBHoJNYoonSHKangGYHwangSGUmHD. Peroxiredoxin 6 promotes lung cancer cell invasion by inducing urokinase-type plasminogen activator via p38 kinase, phosphoinositide 3–kinase, and Akt. Mol Cells2009; 28: 583–8.
26.
JoMYunHMParkKRHee ParkMMyoung KimTHo PakJJae LeeSMoonDCParkCWSongSLeeCKBae HanSTae HongJ. Lung tumor growth-promoting function of peroxiredoxin 6. Free Radic Biol Med2013; 61: 453–63.
27.
WenSTVan EttenRA. The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3 binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity. Genes Dev1997; 1: 2456–67.
FiersWBeyaertRDeclercqWVandenabeeleP. More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene1999; 18: 7719–30.
30.
MatesJMSanchez-JimenezFM. Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol2000; 32: 157–70.
31.
TalleyAKDewhurstSPerrySWDollardSCGummuluruSFineSMNewDEpsteinLGGendelmanHEGelbardHA. Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crma. Mol Cell Biol1995; 15: 2359–66.
32.
FleuryCMignotteBVayssiereJL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie2002; 84: 131–41.
33.
LiLZhangYGChenCL. Anti-apoptotic role of peroxiredoxin III in cervical cancer cells. FEBS Open Bio2013; 3: 51–4.
34.
WangYGLiLLiuCHHongSZhangMJ. Peroxiredoxin 3 is resistant to oxidation-induced apoptosis of Hep-3b cells. Clin Transl Oncol2014; 16: 561–6.
35.
WhitakerHCPatelDHowatWJWarrenAYKayJDSanganTMarioniJCMitchellJAldridgeSLuxtonHJMassieCLynchAGNealDE. Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress. Br J Cancer2013; 109: 983–93.
36.
KwonTRhoJKLeeJCParkYHShinHJChoSKangYKKimBYYoonDYYuDY. An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib. Exp Mol Med2015; 47: 165–165.
37.
WangTDiazAJYenY. The role of peroxiredoxin II in chemoresistance of breast cancer cells. Breast Cancer (Dove Med Press)2014; 6: 73–80.
38.
ChangJWJeonHBLeeJHYooJSChunJSKimJHYooYJ. Augmented expression of peroxiredoxin I in lung cancer. Biochem Biophys Res Commun2001; 289: 507–12.
39.
ParkSHChungYMLeeYSKimHJKimJSChaeHZYooYD. Antisense of human peroxiredoxin II enhances radiation-induced cell death. Clin Cancer Res2000; 6: 4915–20.
40.
DiazAJTamaeDYenYLiJWangT. Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II. Breast Cancer (Dove Med Press)2013; 5: 87–101.
41.
DittmannLMDannerAGronychJWolterMStuhlerKGrzendowskiMBeckerNBageritzJGoidtsVToedtGFelsbergJSabelMCBarbusSReifenbergerGLichterPTewsB. Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro. Oncogene2012; 31: 3409–18.
42.
TochhawngLDengSPervaizSYapCT. Redox regulation of cancer cell migration and invasion. Mitochondrion2013; 13: 246–53.
43.
TobarNVillarVSantibanezJF. Ros-NFκB mediates TGF-β1-induced expression of urokinase-type plasminogen activator, matrix metalloproteinase-9 and cell invasion. Mol Cell Biochem2010; 340: 195–202.
44.
HoJNLeeSBLeeSSYoonSHKangGYHwangSGUmHD. Phospholipase A2 activity of peroxiredoxin 6 promotes invasion and metastasis of lung cancer cells. Mol Cancer Ther2010; 9: 825–32.
45.
QiaoBWangJXieJNiuYYeSWanQYeQ. Detection and identification of peroxiredoxin 3 as a biomarker in hepatocellular carcinoma by a proteomic approach. Int J Mol Med2012; 29: 832–40.
46.
ShiLWuL-LYangJ-RChenX-FZhangYChenZ-QLiuC-LChiS-YZhengJ-YHuangH-XYuF-JLinX-Y. Serum Peroxiredoxin 3 is a useful biomarker for early diagnosis and assessment of prognosis of hepatocellular carcinoma in Chinese patients. Asian Pac J Cancer Prev2014; 15: 2979–86.
47.
HuJXGaoQLiL. Peroxiredoxin 3 is a novel marker for cell proliferation in cervical cancer. Biomed Rep2013; 1: 228–30.
48.
KikutaKTochigiNSaitoSShimodaTMoriokaHToyamaYHosonoASueharaYBeppuYKawaiAHirohashiSKondoT. Peroxiredoxin 2 as a chemotherapy responsiveness biomarker candidate in osteosarcoma revealed by proteomics. Proteomics Clin Appl2010; 4: 560–7.
49.
SharmaSKellyTKJonesPA. Epigenetics in cancer. Carcinogenesis2010; 31: 27–36.
50.
GoldbergADAllisCDBernsteinE. Epigenetics: a landscape takes shape. Cell2007; 128: 635–8.
51.
JonesPABaylinSB. The epigenomics of cancer. Cell2007; 128: 683–92.
52.
SatoFTsuchiyaSMeltzerSJShimizuK. MicroRNAs and epigenetics. FEBS J2011; 278: 1598–609.
53.
ChenQWZhuXYLiYYMengZQ. Epigenetic regulation and cancer (review). Oncol Rep2014; 31: 523–32.
54.
BirdA. DNA methylation patterns and epigenetic memory. Genes Dev2002; 16: 6–21.
55.
JonesPATakaiD. The role of DNA methylation in mammalian epigenetics. Science (New York, NY)2001; 293: 1068–70.
56.
OkanoMXieSLiE. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet1998; 19: 219–20.
57.
OkanoMBellDWHaberDALiE. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell1999; 99: 247–57.
58.
Agrawal-SinghSIskenFAgelopoulosKKleinHUThoennissenNHKoehlerGHascherABaumerNBerdelWEThiedeCEhningerGBeckerASchlenkePWangYMcClellandMKrugUKoschmiederSBuchnerTYuDYSinghSVHansenKServeHDugasMMuller-TidowC. Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene. Blood2012; 119: 2346–57.
59.
SchneiderMSzaumkesselMRichterJAmmerpohlOHansmannMLKuppersRSiebertRGiefingM. The PRDX2 gene is transcriptionally silenced and de novo methylated in hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Blood2014; 123: 3672–4.
60.
PetersonCLLanielM-A. Histones and histone modifications. Curr Biol2004; 14: R546–R51.
61.
DawsonMAKouzaridesT. Cancer epigenetics: from mechanism to therapy. Cell2012; 150: 12–27.
62.
HeintzmanNDHonGCHawkinsRDKheradpourPStarkAHarpLFYeZLeeLKStuartRKChingCWChingKAAntosiewicz-BourgetJELiuHZhangXGreenRDLobanenkovVVStewartRThomsonJACrawfordGEKellisMRenB. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature2009; 459: 108–12.
63.
HebbesTRThorneAWCrane-RobinsonC. A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J1988; 7: 1395–402.
64.
KouzaridesT. Chromatin modifications and their function. Cell2007; 128: 693–705.
65.
ParmigianiRBXuWSVenta-PerezGErdjument-BromageHYanevaMTempstPMarksPA. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci USA2008; 105: 9633–8.
66.
PalandeKKBeekmanRvan der MeerenLEBeverlooHBValkPJTouwIP. The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. PLoS One2011; 6: e16340–e16340.
67.
AmbrosV. The functions of animal microRNAs. Nature2004; 431: 350–5.
68.
CalinGACroceCM. MicroRNA signatures in human cancers. Nat Rev Cancer2006; 6: 857–66.
69.
BartelDP. Micrornas: genomics, biogenesis, mechanism, and function. Cell2004; 116: 281–97.
70.
CalinGADumitruCDShimizuMBichiRZupoSNochEAldlerHRattanSKeatingMRaiKRassentiLKippsTNegriniMBullrichFCroceCM. Frequent deletions and down-regulation of microRNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA2002; 99: 15524–9.
71.
ChenDLiYYuZLiYSuZNiLYangSGuiYLaiY. Downregulated microRNA-510-5p acts as a tumor suppressor in renal cell carcinoma. Mol Med Rep2015; 12: 3061–6.
72.
KapellerJHoughtonLAMonnikesHWalstabJMollerDBonischHBurwinkelBAutschbachFFunkeBLasitschkaFGasslerNFischerCWhorwellPJAtkinsonWFellCBuchnerKJSchmidtmannMvan der VoortIWisserASBergTRappoldGNieslerB. First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome. Hum Mol Genet2008; 17: 2967–77.
73.
GuoQJMillsJNBandurragaSGNogueiraLMMasonNJCampERLarueACTurnerDPFindlayVJ. MicroRNA-510 promotes cell and tumor growth by targeting peroxiredoxin1 in breast cancer. Breast Cancer Res2013; 15: R70–R70.
74.
FindlayVJTurnerDPMoussaOWatsonDK. MicroRNA-mediated inhibition of prostate-derived Ets factor messenger RNA translation affects prostate-derived Ets factor regulatory networks in human breast cancer. Cancer Res2008; 68: 8499–506.
75.
ZhangXGuoGWangGZhaoJWangBYuXDingY. Profile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma. Mol Med Rep2015; 12: 8021–31.
76.
DiaoSZhangJFWangHHeMLLinMCChenYKungHF. Proteomic identification of microRNA-122a target proteins in hepatocellular carcinoma. Proteomics2010; 10: 3723–31.
77.
HeHCZhuJGChenXBChenSMHanZDDaiQSLingXHFuXLinZYDengYHQinGQCaiCChenJHZhongWD. MicroRNA-23b downregulates peroxiredoxin III in human prostate cancer. FEBS Lett2012; 586: 2451–8.
78.
JiangWMinJSuiXQianYLiuYLiuZZhouHLiXGongY. MicroRNA-26a-5p and microRNA-23b-3p up-regulate peroxiredoxin III in acute myeloid leukemia. Leuk Lymphoma2015; 56: 460–71.
79.
GotoYKurozumiAEnokidaHIchikawaTSekiN. Functional significance of aberrantly expressed microRNAs in prostate cancer. Int J Urol2015; 22: 242–52.
80.
LiKKPangJCLauKMZhouLMaoYWangYPoonWSNgHK. Mir-383 is downregulated in medulloblastoma and targets peroxiredoxin 3 (prdx3). Brain Pathol2013; 23: 413–25.
81.
ZhangSWangWGuQXueJCaoHTangYXuXCaoJZhouJWuJDingWQ. Protein and miRNA profiling of radiation-induced skin injury in rats: the protective role of peroxiredoxin-6 against ionizing radiation. Free Radic Biol Med2014; 69: 96–107.
82.
HoshinoIMatsubaraHHanariNMoriMNishimoriTYoneyamaYAkutsuYSakataHMatsushitaKSekiNOchiaiT. Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells. Clin Cancer Res2005; 11: 7945–52.
DaigeCLWigginsJFPriddyLNelligan-DavisTZhaoJBrownD. Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer. Mol Cancer Ther2014; 13: 2352–60.
85.
CraigVJTzankovAFloriMSchmidCABaderAGMullerA. Systemic microRNA-34a delivery induces apoptosis and abrogates growth of diffuse large B-cell lymphoma in vivo. Leukemia2012; 26: 2421–4.
86.
FalahiFvan KruchtenMMartinetNHospersGARotsMG. Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer. Breast Cancer Res2014; 16: 412–412.
87.
RiusMLykoF. Epigenetic cancer therapy: rationales, targets and drugs. Oncogene2012; 31: 4257–65.
88.
RivenbarkAGStolzenburgSBeltranASYuanXRotsMGStrahlBDBlancafortP. Epigenetic reprogramming of cancer cells via targeted DNA methylation. Epigenetics2012; 7: 350–60.
