High APOBEC3B mRNA Expression Is Associated with Human Papillomavirus Type 18 Infection in Cervical Cancer

Abstract

The APOBEC3 (A3) proteins are cytidine deaminases that exhibit the ability to insert mutations in DNA and/or RNA sequences. APOBEC3B (A3B) has been evidenced as a DNA mutagen with consistent high expression in several cancer types. Data concerning the A3B influence on HPV infection and cervical cancer are limited and controversial. We investigated the role of A3B expression levels in cervical cancer in affected women positive for infection by different HPV types. Tumor biopsies from cancerous uterine cervix were collected from 216 women registered at Hospital do Câncer II of Instituto Nacional de Câncer, and infecting HPV was typed. A3B expression levels were quantified from RNA samples extracted from cervical biopsies using real-time quantitative PCR. Median A3B expression levels were higher among HPV18+ samples when compared to HPV16+ counterparts and were also increased compared to samples positive for other HPV types. In squamous cell carcinoma, HPV18+ samples also showed increased median A3B expression when compared to HPV Alpha-9 species or only to HPV16+ samples. Our findings suggest that A3B expression is differentially upregulated in cervical cancer samples infected with HPV18. A3B could be potentially used as a biomarker for HPV infection and as a prognostic tool for clinical outcomes in the context of cervical cancer.

Changes in intrahost genetic diversity according to lesion severity in longitudinal HPV16 samples

“…50 The relationship between APOBEC3 activity and HPV infections has been extensively studied and has been shown to be intricate and type-specific. 21,36 On the one hand, HPV viral gene expression has been shown to promote APOBEC3 activity through many potential interactions, 51 including triggering DNA damage response pathways to enhance the viral replication and consequently upregulating APOBEC3. 36,51 On the other hand, APOBEC3 functions as a viral restriction factor reducing fitness of HPV, something that is also reflected in the genomes of alpha-HPVs which are strongly depleted of potential APOBEC3-targeted motifs.…”

“…21,36 On the one hand, HPV viral gene expression has been shown to promote APOBEC3 activity through many potential interactions, 51 including triggering DNA damage response pathways to enhance the viral replication and consequently upregulating APOBEC3. 36,51 On the other hand, APOBEC3 functions as a viral restriction factor reducing fitness of HPV, something that is also reflected in the genomes of alpha-HPVs which are strongly depleted of potential APOBEC3-targeted motifs. 36 Our model showed that the number of C to T mutations in a TCA and TCT context, which could correlate with APOBEC3 activity, increased significantly in the normal category over time when compared to high-grade (Figure 2C and Table S6).…”

The role of APOBEC3C in modulating the tumor microenvironment and stemness properties of glioma: evidence from pancancer analysis

“…For instance, while initially thought to restrict HIV infection, A3A and A3G proteins can increase the viral mutational load, thereby reducing infectivity ( 5 ). High levels of A3B have been linked to human papillomavirus type 18 infection in cervical cancer (CESC) ( 6 ), as well as T-cell infiltration and improved outcomes in high-grade ovarian carcinoma (OV) ( 7 ). However, the precise functions and molecular mechanisms of A3s in cancer remain largely unclear, warranting further research.…”

MiR-138–5p inhibits prostate cancer cell proliferation and chemoresistance by targeting APOBEC3B

“…In particular, overexpression and abnormal activation of APOBEC3B contribute to the progression of various cancers, including drug resistance [9] , [10] , [11] . In cervical cancer, high expression of APOBEC3B is associated with infection of HPV-18 and proliferation and hypomethylation of cyclin D1 in cervical cancer cells [ 12 , 13 ]. In hepatocellular carcinoma (HCC), upregulation of APOBEC3B promotes cancer progression by interacting with polycomb repressive complex 2 (PRC2) to modulate the tumour microenvironment [14] .…”