Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions

Abstract

Background: We studied the effect of APOBEC3G on persistent human papillomavirus (HPV) infection and the correlation between APOBEC3G polymorphism and HPV persistent infection and cervical disease progression in Uygur women in China. Material/Methods: From January 2015 to December 2017, we enrolled 529 Uygur ethnic group patients with HPV infection. SIHA cells were transfected with APOBEC3G. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect mRNA and protein expression levels of APOBEC3G and HPV E6 and p53. Exon 3 of APOBEC3G was sequenced by first-generation sequencing. Results: The mRNA and protein expression levels of APOBEC3G in the cervical cancer group were significantly higher than in the cervical intraepithelial neoplasia (CIN) group (p<0.05). The mRNA and protein expression levels of APOBEC3G in the CIN group were significantly higher than in the non-cervical lesions group (p<0.05). The mRNA and protein expression levels of HPV E6 in SIHA cells transfected with APOBEC3G were significantly lower than in the control group and the no-load group (p<0.05), and the mRNA and protein expression levels of p53 were significantly higher than in the control group and the no-load group (p<0.05). There was a polymorphic locus rs5757465 on exon 3 of APOBEC3G in Uygur women, and this rare CC type was a risk factor for cervical lesions and cervical cancer (OR=3.714, 95%CI: 1.916-7.202, p<0.05). Conclusions: APOBEC3G is involved in continuous HPV infection, cervical prelesions, and the development of cervical cancer, and the rare genotype (CC) of APOBEC3G may be one of the factors causing cervical lesions in Uygur women who have HPV infection.

HPV‐16/18 E6‐induced APOBEC3B expression associates with proliferation of cervical cancer cells and hypomethylation of Cyclin D1

“…It inhibits the transcription and expression of oncogene HPV E6 and upregulates the transcription and expression of oncogene p53 in Siha cells. since there was reported that the higher levels of APOBEC3B are likely to be associated with the higher frequencies of mutations in some cancer types, it is essential to gain a general profile of the main mutations resulting from APOBEC3B cytosine deamination in different cervical cancer lines 62 . Third, contrary to our findings, APOBEC3A expression was previously reported to be lower in cervical cancer tissues than in normal tissues 63 .…”

Increased RBPs associated with HPV play a role in reducing the survival of patients with head and neck cancer

“…Previous studies have shown that the expression level of APOBECs 3A, 3B, 3C, and 3G is highly expressed in multiple myeloma (24). Furthermore, the mRNA level of APOBEC3G was highly expressed in cervical cancer (25). Moreover, a previous study displayed that the expression of APOBEC3G in the hepatic metastases was noticeably higher than that in the paired primary colon cancer tissues.…”

Regulation of processing bodies: From viruses to cancer epigenetic machinery

“…The encoded protein has been found to be a specific inhibitor of human immunodeficiency virus‐1 (HIV‐1). It is found in cervical prelesions and implicated in the development of cervical cancer (Sui et al, 2019). It inhibits the transcription and expression of oncogene HPVE6 (Human papillomavirus gene E6) and upregulates the transcription and expression of oncogene TP53.…”

“…This belongs to the TET protein (tumor suppressor genes) family, which is found to be highly methylated in gastric cancer (Figure 3; Table 2). Also, overexpression of cytotoxin‐associated gene A (Cag A) significantly decreased the expression of TET protein in gastric patients (Sui et al, 2019; Zhang et al, 2019). APOBEC3G is a P body component (Zheng et al, 2015).…”