Roles of Foxp3 in the Occurrence and Development of Cervical Cancer

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 Oct 15

PMID 26464616

Citations 33

Authors

Qingshuang Luo

Shulan Zhang

Heng Wei

Xiaoao Pang

Huijie Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to evaluate the relationship between forkhead box P3 (Foxp3) expression and clinicopathological characteristics of cervical cancer and to explore the influence of Foxp3 on the biological behaviors of cervical cancer cells.

Methods: In this study, immunohistochemistry, lentivirus mediated transfection, Transwell assay; CCK-8 assay, real-time PCR and flow cytometry were employed to confirm the roles of Foxp3 in the occurrence and development of cervical cancer.

Results: Foxp3 and p16(INK4a) were highly expressed in the cervical cancer and their expressions were related to the FIGO stage, tumor size, lymph node metastasis and serum SCC. Foxp3 had a high expression in the cervical cancer cells, tumor interstitium and metastatic lymph nodes. Foxp3 expression was positively related to p16(INK4a) expression in the cervical cancer. Foxp3 expression in the cervical cancer was negatively related to the prognosis: high Foxp3 expression predicted a poor prognosis. Silencing of Foxp3 was able to inhibit the proliferation and invasiveness of cervical cancer cells, promote their apoptosis, and induce the change in cell cycle. Silencing of Foxp3 also reduced the mRNA and protein expressions of p16(INK4a) in cervical cancer cells.

Conclusion: Foxp3 is highly expressed in the cervical cancer, and able to facilitate the proliferation and invasiveness of cervical cancer, change cell cycle and inhibit their apoptosis, resulting in the occurrence, development and metastasis of cervical cancer.

Citing Articles

Upregulation of long non-coding RNA ENSG00000267838 is related to the high risk of progression and non-response to chemoradiotherapy treatment for cervical cancer.

Custodio Dias Duarte B, Ribeiro Queiroz F, Percinio Costa A, Borges de Melo Neto A, Pereira de Souza Melo C, de Oliveira Salles P Noncoding RNA Res. 2024; 11:104-114.

PMID: 39736855 PMC: 11683307. DOI: 10.1016/j.ncrna.2024.10.004.

FOXP3 serum concentration; a likely predictor of CIN and cervical cancer: Secondary analysis from a case control study at a clinic in South western Uganda.

Ssedyabane F, Niyonzima N, Ngonzi J, Nambi Najjuma J, Mudondo H, Okeny C Gynecol Oncol Rep. 2024; 55:101466.

PMID: 39156036 PMC: 11328032. DOI: 10.1016/j.gore.2024.101466.

Exploring the Role of E6 and E7 Oncoproteins in Cervical Oncogenesis through MBD2/3-NuRD Complex Chromatin Remodeling.

Fudulu A, Diaconu C, Iancu I, Plesa A, Albulescu A, Bostan M Genes (Basel). 2024; 15(5).

PMID: 38790189 PMC: 11121560. DOI: 10.3390/genes15050560.

Mucosal T-cell responses to chronic viral infections: Implications for vaccine design.

Al-Talib M, Dimonte S, Humphreys I Cell Mol Immunol. 2024; 21(9):982-998.

PMID: 38459243 PMC: 11364786. DOI: 10.1038/s41423-024-01140-2.

Identification of FOXP3 epithelial cells contributing to pancreatic proliferation and angiogenesis.

Gong R, Chen X, Sun X, Zhang Y, Wang J, Yu Q Am J Physiol Cell Physiol. 2023; 326(1):C294-C303.

PMID: 38047300 PMC: 11192472. DOI: 10.1152/ajpcell.00461.2023.

References

Fontenot J, Gavin M, Rudensky A . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4):330-6. DOI: 10.1038/ni904. View

Hori S, Sakaguchi S . Foxp3: a critical regulator of the development and function of regulatory T cells. Microbes Infect. 2004; 6(8):745-51. DOI: 10.1016/j.micinf.2004.02.020. View

Curiel T, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P . Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004; 10(9):942-9. DOI: 10.1038/nm1093. View

Sakaguchi S . Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005; 6(4):345-52. DOI: 10.1038/ni1178. View

Tsai H, Wu C, Lai H, Li R, Tung Y, Chuang H . Association between quantitative high-risk human papillomavirus DNA load and cervical intraepithelial neoplasm risk. Cancer Epidemiol Biomarkers Prev. 2005; 14(11 Pt 1):2544-9. DOI: 10.1158/1055-9965.EPI-05-0240. View

Ma G, Miao Q, Liu Y, Gao H, Lian J, Wang Y . High FoxP3 expression in tumour cells predicts better survival in gastric cancer and its role in tumour microenvironment. Br J Cancer. 2014; 110(6):1552-60. PMC: 3960619. DOI: 10.1038/bjc.2014.47. View

Ordi J, Sagasta A, Munmany M, Rodriguez-Carunchio L, Torne A, Del Pino M . Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy. Cancer Cytopathol. 2014; 122(3):227-35. DOI: 10.1002/cncy.21366. View

Lin J, Albers A, Qin J, Kaufmann A . Prognostic significance of overexpressed p16INK4a in patients with cervical cancer: a meta-analysis. PLoS One. 2014; 9(9):e106384. PMC: 4154680. DOI: 10.1371/journal.pone.0106384. View

Parkin D, Bray F . Chapter 2: The burden of HPV-related cancers. Vaccine. 2006; 24 Suppl 3:S3/11-25. DOI: 10.1016/j.vaccine.2006.05.111. View

10.

Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B . Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007; 132(7):2328-39. DOI: 10.1053/j.gastro.2007.03.102. View

11.

Rodriguez A, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle P . Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst. 2008; 100(7):513-7. PMC: 3705579. DOI: 10.1093/jnci/djn044. View

12.

Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T . Foxp3 expression in human cancer cells. J Transl Med. 2008; 6:19. PMC: 2386447. DOI: 10.1186/1479-5876-6-19. View

13.

Sakaguchi S, Yamaguchi T, Nomura T, Ono M . Regulatory T cells and immune tolerance. Cell. 2008; 133(5):775-87. DOI: 10.1016/j.cell.2008.05.009. View

14.

Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, Gillio-Tos A, De Marco L . Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial. Lancet Oncol. 2008; 9(10):937-45. DOI: 10.1016/S1470-2045(08)70208-0. View

15.

Sakaguchi S, Miyara M, Costantino C, Hafler D . FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010; 10(7):490-500. DOI: 10.1038/nri2785. View

16.

Ladoire S, Arnould L, Mignot G, Coudert B, Rebe C, Chalmin F . Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2010; 125(1):65-72. DOI: 10.1007/s10549-010-0831-1. View

17.

Kerdiles Y, Stone E, Beisner D, Beisner D, McGargill M, Chen I . Foxo transcription factors control regulatory T cell development and function. Immunity. 2010; 33(6):890-904. PMC: 3034255. DOI: 10.1016/j.immuni.2010.12.002. View

18.

Arbyn M, Castellsague X, de Sanjose S, Bruni L, Saraiya M, Bray F . Worldwide burden of cervical cancer in 2008. Ann Oncol. 2011; 22(12):2675-2686. DOI: 10.1093/annonc/mdr015. View

19.

Hou F, Ma D, Cui B . Treg cells in different forms of uterine cancer. Clin Chim Acta. 2012; 415:337-40. DOI: 10.1016/j.cca.2012.11.004. View

20.

Ma G, Chen S, Sun Z, Miao Q, Liu Y, Zeng X . FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway. Biochem Biophys Res Commun. 2012; 430(2):804-9. DOI: 10.1016/j.bbrc.2012.11.065. View