OBSTETRICS AND GYNAECOLOGY / BASIC RESEARCH
Up-regulation of peroxiredoxin 3 by high-risk human papillomavirus in cervical cancer cells
More details
Hide details
1
Department of Laboratory Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
2
Department of Histology and Embryology, Binzhou Medical University, Binzhou, China
3
Department of Obstetrics and Gynecology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
Submission date: 2020-04-16
Final revision date: 2020-07-19
Acceptance date: 2020-08-02
Online publication date: 2021-04-18
Publication date: 2026-06-30
Corresponding author
Lianqin Li
Department of Obstetrics and Gynecology
Yantai Affiliated Hospital of Binzhou Medical University,
717 Jinbu St
Muping District,
264100, Yantai, China
Arch Med Sci 2026;22(3):1804-1810
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Peroxiredoxin 3 (PRX3) is a member of the PRX family with antioxidant functions by scavenging hydrogen peroxide. Since the development of cervical cancer is causally linked to high-risk human papillomavirus (HPV) that induces oxidative stress, we conducted the present study to investigate the response of PRX3 to high-risk HPV infection.
Material and methods:
This study included fifty-six patients with invasive squamous cervical cancer and sixty control patients with hysteromyoma. Enzyme-linked immunosorbent assay was performed to detect cervical oxidative stress and serum PRX3. The expression of PRX3 and oncoprotein E6 of HPV16 or HPV18 was examined in cervical cancer tissues by immunohistochemistry. Western blot was applied to detect the expression of PRX3 and E6 in cervical cancer cell lines including CaSki, HeLa, and C33A.
Results:
Patients with cervical cancer showed higher serum PRX3 than control patients with hysteromyoma. Levels of oxidative markers in cervical cancer tissues were elevated as compared to normal cervical epithelia. PRX3 expression was upregulated in cervical cancer tissues and the upregulation was positively associated with the expression of E6 of HPV16 or HPV18. The association was confirmed in HPV-containing cervical cancer cell lines including CaSki and HeLa.
Conclusions:
Our results indicated a positive response of PRX3 to HPV-induced oxidative stress. Serum PRX3 might be a potential indicator of active amplification of high-risk HPV in cervical cancer cells.
REFERENCES (28)
1.
Matsushima S, Ide T, Yamato M, et al. Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 2006; 113: 1779-86.
2.
Chua PJ, Lee EH, Yu Y, et al. Silencing the peroxiredoxin III gene inhibits cell proliferation in breast cancer. Int J Oncol 2010; 36: 359-64.
3.
Wonsey DR, Zeller KI, Dang CV. The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc Natl Acad Sci USA 2002; 99: 6649-54.
4.
Kim K, Yu M, Han S, et al. Expression of human peroxiredoxin isoforms in response to cervical carcinogenesis. Oncol Rep 2009; 21: 1391-6.
5.
Hu JX, Gao Q, Li L. Peroxiredoxin 3 is a novel marker for cell proliferation in cervical cancer. Biomed Rep 2013; 1: 228-30.
6.
Williams VM, Filippova M, Filippov V, Payne KJ, Duerksen-Hughes P. Human papillomavirus type 16 E6* induces oxidative stress and DNA damage. J Virol 2014; 88: 6751-61.
7.
Chen Wongworawat Y, Filippova M, Williams VM, Filippov V, Duerksen-Hughes PJ. Chronic oxidative stress increases the integration frequency of foreign DNA and human papillomavirus 16 in human keratinocytes. Am J Cancer Res 2016; 6: 764-80.
8.
Marullo R, Werner E, Zhang H, Chen GZ, Shin DM, Doetsch PW. HPV16 E6 and E7 proteins induce a chronic oxidative stress response via NOX2 that causes genomic instability and increased susceptibility to DNA damage in head and neck cancer cells. Carcinogenesis 2015; 36: 1397-406.
9.
Safaeian M, Hildesheim A, Gonzalez P, et al. Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PLoS One 2012; 7: e33619.
10.
Li L, Zhang YG, Chen CL. Anti-apoptotic role of peroxiredoxin III in cervical cancer cells. FEBS Open Bio 2013; 3: 51-4.
11.
Lewitowicz P, Nasierowska-Guttmejer A, Rokita W, et al. HPV genotyping and p16/Ki-67 test significantly improve detection rate of high-grade cervical squamous intraepithelial lesion. Arch Med Sci 2019; 16: 87-93.
12.
Kaczmarczyk-Sedlak I, Folwarczna J, Sedlak L, et al. Effect of caffeine on biomarkers of oxidative stress in lenses of rats with streptozotocin-induced diabetes. Arch Med Sci 2019; 15: 1073-80.
13.
Abba MC, Laguens RM, Dulout FN, Golijow CD. The c-myc activation in cervical carcinomas and HPV 16 infections. Mutat Res 2004; 557: 151-8.
14.
Veldman T, Liu X, Yuan H, Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci USA 2003; 100: 8211-6.
15.
McMurray HR, McCance DJ. Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. J Virol 2003; 77: 9852-61.
16.
Kim YS, Lee HL, Lee KB, et al. Nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer. Korean J Intern Med 2011; 26: 304-13.
17.
Chiribau CB, Cheng L, Cucoranu IC, Yu YS, Clempus RE, Sorescu D. FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts. J Biol Chem 2008; 283: 8211-7.
18.
Jeong HJ, Jeong HW, Song SS, et al. Upregulation of peroxiredeoxin III in the hippocampus of acute immobilization stress model rats and the Foxo3a-dependent expression in PC12 cells. Cell Mol Neurobiol 2011; 31: 1041-6.
19.
Olmos Y, Sanchez-Gomez FJ, Wild B, et al. SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1alpha complex. Antioxid Redox Signal 2013; 19: 1507-21.
20.
Liu MH, Zhang Y, He J, et al. Upregulation of peroxiredoxin III in doxorubicin-induced cytotoxicity and the FoxO3a-dependent expression in H9c2 cardiac cells. Exp Ther Med 2015; 10: 1515-20.
21.
Cunniff B, Benson K, Stumpff J, et al. Mitochondrial-targeted nitroxides disrupt mitochondrial architecture and inhibit expression of peroxiredoxin 3 and FOXM1 in malignant mesothelioma cells. J Cell Physiol 2013; 228: 835-45.
22.
Song IS, Jeong YJ, Seo YJ, et al. Peroxiredoxin 3 maintains the survival of endometrial cancer stem cells by regulating oxidative stress. Oncotarget 2017; 8: 92788-800.
23.
He HC, Zhu JG, Chen XB, et al. MicroRNA-23b downregulates peroxiredoxin III in human prostate cancer. FEBS Lett 2012; 586: 2451-8.
24.
Li KK, Pang JC, Lau KM, et al. MiR-383 is downregulated in medulloblastoma and targets peroxiredoxin 3 (PRDX3). Brain Pathol 2013; 23: 413-25.
25.
Shi L, Wu LL, Yang JR, et al. Serum peroxiredoxin3 is a useful biomarker for early diagnosis and assessment of prognosis of hepatocellular carcinoma in Chinese patients. Asian Pac J Cancer Prev 2014; 15: 2979-86.
26.
Ismail S, Mayah W, Battia HE, et al. Plasma nuclear factor kappa B and serum peroxiredoxin 3 in early diagnosis of hepatocellular carcinoma. Asian Pac J Cancer Prev 2015; 16: 1657-63.
27.
Liu HL, Li TT, Yu AQ, et al. Plasma level of peroxiredoxin 3 in patients with polycystic ovarian syndrome. BMC Endocr Disord 2019; 19: 32.
28.
Wang L, Hao JM, Yu AQ, et al. The association of plasma peroxiredoxin 3 with insulin in pregnant women. Biochem Biophys Res Commun 2019; 508: 805-10.