Abnormal Methylation of HOXA11 Promoter Promotes Tumor Progression in Testicular Germ Cell Tumor

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2024 Jun 17

PMID 38883380

Authors

Juan He

Liang Li

Shengxin Wang

Shan Wu

Wenli Xiao

Li Li

Li Dong

An Ge

Kaikai Xie

Jiaomin Wang

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the methylation of HOXA11 gene promoter in testicular germ cell tumor (GCT).

Method: The clinicopathological data of 63 patients with primary testicular GCT who underwent surgery during Apr. 2019 to Mar. 2021, were retrospectively analyzed. Their GCT tissue and paraneoplastic testicular tissue were obtained, and genomic DNA was extracted from both. The methylation of HOXA11 gene promoter region was detected by methylation-specific PCR (MSP). The incidence of HOXA11 methylation in testicular GCT and adjacent tissues was compared, and the connection between methylation level in testicular GCT and clinicopathologic features of patients was statistically analyzed. Testicular GCT cells were treated with methylated transferase inhibitor 5-Aza-dC , and HOXA11 mRNA expression was detected by real-time PCR.

Results: The positive rate of HOXA11 promoter methylation in testicular GCT tissues was notably higher than that of paired adjacent tissues (). The abnormal methylation of HOXA11 gene promoter was correlated with lymph node metastasis and TNM stage in patients (). HOXA11 mRNA expression in testicular GCT cells treated with 5-Aza-dC was increased ().

Conclusion: Abnormal methylation of HOXA11 gene promoter in testicular germ cell tumor tissue inhibits transcription and expression of HOXA11 gene. The abnormal methylation of HOXA11 promoter region is tightly associated with lymph node metastasis and TNM staging in testicular germ cell tumors.

Citing Articles

Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer.

Lee S, Oh T, An S, Lee S Dev Reprod. 2024; 28(2):37-45.

PMID: 39055103 PMC: 11268892. DOI: 10.12717/DR.2024.28.2.37.

References

Buskbjerg C, Amidi A, Agerbaek M, Gravholt C, Hosseini S, Zachariae R . Cognitive changes and brain connectomes, endocrine status, and risk genotypes in testicular cancer patients-A prospective controlled study. Cancer Med. 2021; 10(18):6249-6260. PMC: 8446403. DOI: 10.1002/cam4.4165. View

Duan H, Deng T, Chen Y, Zhao Z, Wen Y, Chen Y . Association between vasectomy and risk of testicular cancer: A systematic review and meta-analysis. PLoS One. 2018; 13(3):e0194606. PMC: 5864054. DOI: 10.1371/journal.pone.0194606. View

Marshall C, Enzerra M, Rahnemai-Azar A, Ramaiya N . Serum tumor markers and testicular germ cell tumors: a primer for radiologists. Abdom Radiol (NY). 2018; 44(3):1083-1090. DOI: 10.1007/s00261-018-1846-z. View

Chen X, Zhang J, Ruan W, Huang M, Wang C, Wang H . Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer. J Clin Invest. 2020; 130(12):6278-6289. PMC: 7685755. DOI: 10.1172/JCI139597. View

Xing Z, Li S, Liu Z, Zhang C, Bai Z . CTCF-induced upregulation of HOXA11-AS facilitates cell proliferation and migration by targeting miR-518b/ACTN4 axis in prostate cancer. Prostate. 2020; 80(5):388-398. DOI: 10.1002/pros.23953. View

Priskorn L, Kreiberg M, Bandak M, Lauritsen J, Daugaard G, Petersen J . Testicular cancer survivors have shorter anogenital distance that is not increased by 1 year of testosterone replacement therapy. Hum Reprod. 2021; 36(9):2443-2451. DOI: 10.1093/humrep/deab162. View

Kalavska K, Kucerova L, Schmidtova S, Chovanec M, Mego M . Cancer Stem Cell Niche and Immune-Active Tumor Microenvironment in Testicular Germ Cell Tumors. Adv Exp Med Biol. 2020; 1226:111-121. DOI: 10.1007/978-3-030-36214-0_9. View

Chen X, Wang Y, Ruan M, Li J, Zhong M, Li Z . Treatment of Testicular Relapse of B-cell Acute Lymphoblastic Leukemia With CD19-specific Chimeric Antigen Receptor T Cells. Clin Lymphoma Myeloma Leuk. 2020; 20(6):366-370. PMC: 8312220. DOI: 10.1016/j.clml.2019.10.016. View

Xu Y, Ren Z, Wang X, Ren M . The lncRNA HOXA11-AS acts as a tumor promoter in breast cancer through regulation of the miR-125a-5p/TMPRSS4 axis. J Gene Med. 2022; 24(5):e3413. DOI: 10.1002/jgm.3413. View

10.

You L, Wu Q, Xin Z, Zhong H, Zhou J, Jiao L . The long non-coding RNA HOXA11-AS activates ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Cancer Cell Int. 2021; 21(1):576. PMC: 8556882. DOI: 10.1186/s12935-021-02255-6. View

11.

Xia H, Niu Q, Ding Y, Zhang Z, Yuan J, Jin W . Long noncoding HOXA11-AS knockdown suppresses the progression of non-small cell lung cancer by regulating miR-3619-5p/SALL4 axis. J Mol Histol. 2021; 52(4):729-740. DOI: 10.1007/s10735-021-09981-1. View

12.

Leao R, Ahmad A, Hamilton R . Testicular Cancer Biomarkers: A Role for Precision Medicine in Testicular Cancer. Clin Genitourin Cancer. 2018; 17(1):e176-e183. DOI: 10.1016/j.clgc.2018.10.007. View

13.

Cheng Y, Xiong H, Li Y, Zuo H, Liu Y, Liao G . LncRNA HOXA11-AS promotes cell growth by sponging miR-24-3p to regulate JPT1 in prostate cancer. Eur Rev Med Pharmacol Sci. 2021; 25(14):4668-4677. DOI: 10.26355/eurrev_202107_26377. View

14.

Saghafinia S, Mina M, Riggi N, Hanahan D, Ciriello G . Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors. Cell Rep. 2018; 25(4):1066-1080.e8. DOI: 10.1016/j.celrep.2018.09.082. View

15.

Ge F, Tie W, Zhang J, Zhu Y, Fan Y . Expression of the HOXA gene family and its relationship to prognosis and immune infiltrates in cervical cancer. J Clin Lab Anal. 2021; 35(11):e24015. PMC: 8605136. DOI: 10.1002/jcla.24015. View

16.

Liang W, Zhao Y, Huang W, Gao Y, Xu W, Tao J . Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA). Theranostics. 2019; 9(7):2056-2070. PMC: 6485294. DOI: 10.7150/thno.28119. View

17.

He Y, Qiu X . Suppression of lncRNA HOXA11-AS/miR-124 Axis Inhibits Glioma Progression. Cell Biochem Biophys. 2021; 79(4):815-822. DOI: 10.1007/s12013-021-01007-7. View

18.

Misawa A, Kondo Y, Takei H, Takizawa T . Long Noncoding RNA and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes in Prostate Cancer. Genes (Basel). 2021; 12(2). PMC: 7912412. DOI: 10.3390/genes12020182. View

19.

Gao M, Li H, Bi Y, Zhang Z, Wang S, Li J . The Polymorphisms of lncRNA HOXA11-AS and the risk of Lung Cancer in Northeastern Chinese population. J Cancer. 2020; 11(3):592-598. PMC: 6959036. DOI: 10.7150/jca.35411. View

20.

Widmeier E, Fullgraf H, Waller C . Complete remission of Cdx-2 positive primary testicular carcinoid tumor: 10-years follow-up and literature review. BMC Urol. 2020; 20(1):197. PMC: 7737363. DOI: 10.1186/s12894-020-00768-2. View