APOBEC3B (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3B)

Furthermore, A3B depletion resulted in over a 50% reduction of DNA breaks along with altered expression of DNA damage repair proteins. This study demonstrates that A3B is an inducer of R-loop formation and DNA damage in HPV positive cells, thereby regulating cellular and viral gene expression along with HPV replication.

APOBEC3-mediated mutagenesis is discussed as a mechanistic link between genomic instability and tumor-immune crosstalk in solid tumors, with emphasis on its relationships to immunoediting, immune checkpoint pathways, and therapeutic responses. Context-dependent associations of APOBEC3 activity with immune activation or immune evasion are also considered, together with their implications for strategies that modulate this pathway.

Furthermore, BER-mediated processing of A3B-induced uracil bases contributes to the formation of R-loop-associated DSBs, which are essential for ER-regulated gene activation. These findings establish a role for A3B in R-loop homeostasis and transcriptional regulation, with implications for understanding ER-driven genomic instability and potential therapeutic targeting of A3B.

Consistent with tumor data, RNA-seq showed upregulation of tumor enhancing pathways only in cells that enhanced tumor progression. The results indicate that in a breast cancer xenograft model, APOBEC3A and APOBEC3H Haplotype I are more likely to contribute to enhanced tumor progression than APOBEC3B.

Surprisingly, we find that human A3B is incapable of blocking the replication of a murine papillomavirus (Mus musculus papillomavirus 1, MmuPV1) in relevant primary cells from these animals or in infected tissues in vivo. These findings highlight the complexity of teasing apart host-pathogen interactions and suggest that papillomaviruses may have a general mechanism for escaping restriction by antiviral enzymes, such as A3B.

Finally, the signature was associated with worse overall survival in pancreatic cancer (HR 5.9) and lesser effects in stomach, lung, and cervical cancers. These results shed light on the interplay of TE activities, DNA repair, and genome instability in human cancers.

These findings indicate the critical role of ferroptosis and glutathione metabolism in the development and progression of ESCC. Meanwhile, APOBEC3B may serve as a promising therapeutic target for cisplatin-resistant ESCC cells.

The synthesized evidence suggests that high-risk HPV types are present in a subset of breast cancers worldwide, but with lower viral loads compared to cervical cancer, indicating a potentially different mode of action. The association between HPV and breast cancer warrants further rigorous investigation to clarify its clinical and preventive implications.

Silencing APOBEC3B reduced RPA2 and ASF1B levels and suppressed TGF-β signaling. These findings identify APOBEC3B/ASF1B as a central pathway through which HPV infection activates TGF-β signaling and promotes EMT, offering potential biomarkers and therapeutic targets for high-risk HPV-positive OPC.

This infiltration may be mediated by cytokines and chemokines. Collectively, these findings suggest that A3B holds potential as a novel prognostic biomarker and immunotherapeutic target for PCa.