Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population

Abstract

A case-control study was used to explore the association between the methylation status in the promoter regions of the cGAS, MAVS, and TRAF3 genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The cGAS, MAVS, and TRAF3 promoter methylation levels in CPL (CPLcGAS = 35.40%, CPLMAVS = 24.26%, and CPLTRAF3 = 96.76%) were significantly higher than those in the control (ControlcGAS = 31.87%, ControlMAVS = 21.16%, and ControlTRAF3 = 96.26%, PcGAS< 0.001, PMAVS< 0.001, and PTRAF3 = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose cGAS methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (ORa = 2.49, 95% CI = 1.31-4.75, Pa = 0.006). The women with MAVS methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (ORa = 1.97, 95% CI = 1.06–3.69, Pa = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of cGAS and MAVS in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in cGAS, MAVS, and TRAF3 genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in cGAS and MAVS genes and hrHPV infection might play a role in the development of CPL.

Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens

“…DNA methylation of host genes and HPV-related genes in cervical epithelium played an important role in the diagnosis and treatment of cervical lesions [ 8 , 11 , 32 – 34 ]. In this study, we determined the value of DNA methylation marker panel ( ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671 ) in detection of CIN lesions on cervical biopsy specimens.…”

“…The methylation level of more than 100 host genes is related to cervical cancer. Studies have found that CADM1, CDH1, DAPK1, EPB4L3, FAM19A4, MAL, PAX1, PRDM14 and TERT are among the most commonly methylated genes in cervical cancer and precancerous lesions [ 2 , 11 – 15 ]. At present, host cell DNA methylation analysis is mainly used for preliminary triage of hrHPV-positive women to detect cervical cancer and advanced CIN [ 8 ].…”

An Improved, Dual-Direction, Promoter-Driven, Reverse Genetics System for the Infectious Bursal Disease Virus (IBDV)

“…Arginine methylation, a classified protein post-translational modification, is mediated by a member protein arginine methyltransferase, which furtherly regulates multiple signaling pathways [ 29 , 30 ]. Recently, it has been suggested that arginine methylation plays a critical role in regulating the replication of many viruses [ 31 , 32 ].…”

Diagnostic Value of the Hypomethylation of the <i>WISP1</i> Promoter in Patients with Hepatocellular Carcinoma Associated with Hepatitis B Virus

“…The reference promoter sequence for the human WISP1 gene was obtained from the UCSC human genome browser and Ensembl genome browser, which is the widely recognized public platform for searching gene promoter sequence (Kent et al 2002;Aken et al 2017;Chadaeva et al 2019;Huang et al 2019). The methylated (M) and unmethylated (U) WISP1 promoter-specific primers were designed by MethPrimer following its published standards (Li and Dahiya 2002).…”