Abstract
Peroxiredoxins (Prdxs) play important roles in cell proliferation, differentiation, and the mediation of intracellular signalling pathways. Prdx2 is an important member of the peroxiredoxin family and is upregulated in many cancers. Until now, the biological functions of Prdx2 in gastric cancer have not been completely understood, and the underlying mechanisms remain elusive. The aim of this study was to identify the role of Prdx2 on the growth of gastric cancer cells and the underlying mechanisms. We demonstrated that Prdx2 was highly expressed in gastric cancer tissues and cell lines and that the over-expression of Prdx2 correlated with the progression of gastric cancer. Further, Prdx2 was silenced with a specific, lentiviral vector-mediated shRNA, and this suppressed the proliferation of gastric cancer cells and promoted the apoptosis of gastric cancer cells. Finally, the knockdown of Prdx2 contributed to the attenuated gastric cancer growth in BALB/c nude mice. In conclusion, these findings demonstrate that Prdx2 may participate in the carcinogenesis and development of gastric cancer.
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Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014 [J]. CA Cancer J Clin 64(1):9–29
Hu B, El Hajj N, Sittler S et al (2012) Gastric cancer: classification, histology and application of molecular pathology [J]. J Gastrointest Oncol 3(3):251–261
Gotoda T, Kusano C, Moriyasu F (2014) Future perspective of gastric cancer endotherapy [J]. Ann Transl Med 2(3):25
Roessner A, Kuester D, Malfertheiner P et al (2008) Oxidative stress in ulcerative colitis-associated carcinogenesis [J]. Pathol Res Pract 204(7):511–524
Devasagayam TP, Tilak JC, Boloor KK et al (2004) Free radicals and antioxidants in human health: current status and future prospects [J]. J Assoc Physicians India 52:794–804
Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress [J]. Curr Biol 24(10):R453–r462
Poole LB (2011) Overview of Peroxiredoxins in oxidant defense and redox regulation [J]. Chapter (Unit7.9)
Memon AA, Chang JW, Oh BR, Yoo YJ (2005) Identification of differentially expressed proteins during human urinary bladder cancer progression [J]. Cancer Detect Prev 29(3):249–255
Jarvela S, Rantala I, Rodriguez A et al (2010) Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors [J]. BMC Cancer 10:104
Karihtala P, Mantyniemi A, Kang SW et al (2003) Peroxiredoxins in breast carcinoma [J]. Clin Cancer Res 9(9):3418–3424
Wu XY, Fu ZX, Wang XH (2010) Peroxiredoxins in colorectal neoplasms [J]. Histol Histopathol 25(10):1297–1303
Lee KW, Lee DJ, Lee JY, Kang DH, Kwon J, Kang SW (2011) Peroxiredoxin II restrains DNA damage-induced death in cancer cells by positively regulating JNK-dependent DNA repair [J]. J Biol Chem 286(10):8394–8404
Park SH, Chung YM, Lee YS, Kim HJ, Kim JS, Chae HZ, Yoo YD (2000) Antisense of human peroxiredoxin II enhances radiation-induced cell death [J]. Clin Cancer Res 6(12):4915–4920
Parmigiani RB, Xu WS, Venta-Perez G, Erdjument-Bromage H, Yaneva M, Tempst P, Marks PA (2008) HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation [J]. Proc Natl Acad Sci U S A 105(28):9633–9638
Lu W, Fu Z, Wang H, Feng J, Wei J, Guo J (2014) Peroxiredoxin 2 is upregulated in colorectal cancer and contributes to colorectal cancer cells' survival by protecting cells from oxidative stress [J]. Mol Cell Biochem 387(1–2):261–270
Lu W, Fu Z, Wang H, Feng J, Wei J, Guo J (2014) Peroxiredoxin 2 knockdown by RNA interference inhibits the growth of colorectal cancer cells by downregulating Wnt/beta-catenin signaling [J]. Cancer Lett 343(2):190–199
Wang S, Chen Z, Zhu S et al (2019) PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer [J]. Redox Biol 28:101319
Yang SF, Ma R, Pan LL, Cao J, Sheng N (2018) RKIP and peroxiredoxin 2 expression predicts the proliferative potential of gastric cancer stem cells [J]. Oncol Lett 15(3):3173–3177
Hanschmann EM, Godoy Jé R, Berndt C et al (2013) Thioredoxins, Glutaredoxins, and Peroxiredoxins—molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling [J]. Antioxid Redox Signal 19(13):1539–1605
Lomnytska MI, Becker S, Bodin I, Olsson A, Hellman K, Hellström AC, Mints M, Hellman U, Auer G, Andersson S (2011) Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value [J]. Br J Cancer 104(1):110–119
Yue HY, Cao J, Cui JF, Dai Z, Su JJ, Duan XX, Yang C, Yue HF, Li Y, Liu YK (2007) The expression of peroxiredoxin II in hepatocellular carcinoma and its significance [J]. Zhonghua Gan Zang Bing Za Zhi 15(5):366–369
Rhee SG, Woo HA (2011) Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H(2)O(2), and protein chaperones [J]. Antioxid Redox Signal 15(3):781–794
Oláhová M, Veal EA (2015) A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity [J]. Aging Cell 14(4):558–568
Neumann CA, Fang Q (2007) Are peroxiredoxins tumor suppressors? [J]. Curr Opin Pharmacol 7(4):375–380
Hirahashi M, Koga Y, Kumagai R, Aishima S, Taguchi K, Oda Y (2014) Induced nitric oxide synthetase and peroxiredoxin expression in intramucosal poorly differentiated gastric cancer of young patients [J]. Pathol Int 64(4):155–163
Hu X, Weng Z, Chu CT, Zhang L, Cao G, Gao Y, Signore A, Zhu J, Hastings T, Greenamyre JT, Chen J (2011) Peroxiredoxin-2 protects against 6-hydroxydopamine-induced dopaminergic neurodegeneration via attenuation of the ASK1 signaling cascade [J]. J Neurosci 31(1):247–261
Ishii T, Warabi E, Yanagawa T (2012) Novel roles of peroxiredoxins in inflammation, cancer and innate immunity [J]. J Clin Biochem Nutr 50(2):91–105
Yang C, Fu Z (2014) Liposomal delivery and polyethylene glycol-liposomal oxaliplatin for the treatment of colorectal cancer (review) [J]. Biomed Rep 2(3):335–339
Walters J, Pop C, Scott FL et al (2009) A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis [J]. Biochem J 424(Pt 3):335–345
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Zhang, S., He, J., Tang, M. et al. Prdx2 Upregulation Promotes the Growth and Survival of Gastric Cancer Cells. Pathol. Oncol. Res. 26, 1869–1877 (2020). https://doi.org/10.1007/s12253-019-00783-1
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DOI: https://doi.org/10.1007/s12253-019-00783-1