APOBEC-mediated genomic alterations link immunity and viral infection during human papillomavirus-driven cervical carcinogenesis

Lanting, C.I.; Zhang, Na; Wang, Mingyan; Li, Da‐Jin; Du, Yan

doi:10.5582/bst.2017.01103

Cited by 17 publications

(17 citation statements)

References 42 publications

(60 reference statements)

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“…APOBEC3B is hypothesized to be the principal cancer driver of A3-catalyzed somatic mutations, and plays a prominent role in the genesis and evolution of various cancers. As part of the innate immune system, which plays a key role in combating exogenous infection especially viral infection, APOBEC3B expression is stimulated by a complex network of innate immune responses involving components such as interferons, interleukins, and Toll-like receptors [ 7 ]. APOBEC3B can cause C-to-T transition in carcinogenesis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…In humans, the AID/APOBEC family has eleven members including activation-induced cytidine deaminase (AID, gene name: AICDA ), and apolipoprotein B mRNA editing enzymes, catalytic polypeptide-like [APOBECs: APOBEC1 (A1), APOBEC2 (A2), APOBEC3 (A3), APOBEC3A (A3A), APOBEC3B (A3B), APOBEC3C (A3C), APOBEC3DE (A3DE), APOBEC3F (A3F), APOBEC3G (A3G), APOBEC3H (A3H), and APOBEC4 (A4)] [ 7 ]. It can specifically edit DNA or RNA through the irreversible cytidine and deoxycytidine deamination, causing the conversion of target cytosine (C) to uracil (U), and consequently causing DNA or RNA alterations/damages [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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APOBEC3B up-regulation independently predicts ovarian cancer prognosis: a cohort study

Tao

et al. 2018

Cancer Cell Int

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BackgroundOvarian cancer is a heterogeneous disease with a high degree of genomic instability, pro-/antitumor immunity and inflammation, and remains the most lethal gynecologic cancer worldwide. APOBEC3B, a member of the AID/APOBEC family, is part of the innate immune system which plays a key role in combating exogenous infection especially viral infection. Studies have shown that APOBEC3B expression is elevated in a variety of cancer tissues and cell lines, and plays a prominent role in the genesis and evolution of various cancers. However, the clinical relevance of APOBEC3B in ovarian cancer needs to be further investigated. The current study aimed to evaluate the predictive value of APOBEC3B in ovarian cancer clinical outcome, and to explore possible molecular mechanisms contributing to ovarian cancer progression.MethodsThe expression of APOBEC3B in biopsy tissue specimens from 88 ovarian cancer patients was examined using immunohistochemistry. In addition, ovarian cancer cell lines were transfected with APOBEC3B siRNA or pLenti-APOBEC3B construct. Western blotting and SRB assay were performed to explore the role of APOBEC3B in ovarian cancer.ResultsPatients were followed for a median of 74.77 months following the time of surgery. Forty-two patients had died, 5 had relapsed but were still alive at the end of study, and 41 patients remained alive and had no recurrence. Over-expression of APOBEC3B was associated with advanced FIGO stage and elevated CA125 (both p< 0.05). Univariate analysis result showed that histological subtype, FIGO stage, intravascular tumor thrombus, CA125 and APOBEC3B expression were associated with overall survival and disease-free survival of ovarian cancer patients. Multivariate analysis result showed that higher APOBEC3B expression were an independent prognostic factor to predict both worse overall survival (hazard ratio: 5.18, 95% confidence interval: 1.40–11.95, p= 0.003) and disease-free survival (hazard ratio: 4.23, 95% confidence interval: 1.60–11.17, p= 0.004) of ovarian cancer patients. Furthermore, knockdown of APOBEC3B expression in ovarian cancer cells caused an decrease in cell line viability.ConclusionsAPOBEC3B expression is an independent prognostic factor in ovarian cancer patients. Knockdown of APOBEC3B expression affects ovarian cancer viability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

APOBEC3B up-regulation independently predicts ovarian cancer prognosis: a cohort study

Tao

et al. 2018

Cancer Cell Int

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“…This may lead to somatic hypermutations at the IgH locus of B-lymphocytes and consequently induce progression of EBV-infected B-lymphocytes into neoplastic B-cells (lymphomas) ( 18 ). Similarly, Chen et al demonstrated the importance of APOBEC enzymes in mediating the complex interactions between HPV infection, host immune system, and cervix during cervical cancer progression ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

“…Several recent studies also highlight novel mechanisms on the complex interplay between viruses (including EBV and HPV), immune system, and carcinogenesis. Among these, apolipoprotein B mRNA editing enzymes (APOBEC) family of deaminases appears to play a prominent role ( 17 , 18 ). APOBEC family of enzymes, involved in the editing of DNA and/or RNA sequences, acts on the inner immune system against viruses and endogenous retroelements ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Epstein–Barr Virus in Cervical Cancer: A Brief Update

et al. 2018

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Epstein–Barr virus (EBV) belongs to the group of gamma-herpes viruses and was the first recognized human oncovirus. EBV is responsible for infectious mononucleosis and multiple lymphoid and epithelial malignancies including B-cell lymphomas (Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorder), various T-cell/NK lymphoproliferative disorders, nasopharyngeal carcinoma, and gastric carcinoma, respectively. In addition, the presence of EBV has been documented in other cancers including breast, prostate, oral, and salivary gland carcinomas. The presence and role of EBV in cervical cancer and its precursor lesions (CIN) have also been described, but the results from the literature are inconsistent, and the causal role of EBV in cervical cancer pathogenesis has not been established yet. In the present review, we briefly surveyed and critically appraised the current literature on EBV in cervical cancer and its variants (lymphoepithelioma-like carcinoma) as well as its precursor lesions (CIN). In addition, we discussed the possible interactions between EBV and human papilloma virus as well as between EBV and immune checkpoint regulators (PD-L1). Though further studies are needed, the available data suggest a possible causal relationship between EBV and cervical cancer pathogenesis.

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“…Whereas in HPV(+) HNSCC, it is predominated by the APOBEC signature, indicating a mutagenic mechanism due to viral infection, tissue inflammation or retrotransposon activity [ 55 , 56 ]. Chen et al also reported the APOBEC signature as the major mutational signature for HPV(+) cervical cancer [ 57 ]. These findings implicate a clear etiologic contribution by HPV via APOBEC-mediated mutagenesis, which is different from the defective DNA mismatch repair signature contributed by EBV in NPC.…”

Section: Genomic Characterizations Of Ebv(+) Npc and Hpv(+) Hnscc mentioning

confidence: 99%

Genomic Landscapes of EBV-Associated Nasopharyngeal Carcinoma vs. HPV-Associated Head and Neck Cancer

Ngan

Wang

et al. 2018

Cancers

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Epstein-Barr virus-positive nasopharyngeal carcinoma (EBV(+) NPC), and human papillomavirus-positive head and neck squamous cell carcinoma (HPV(+) HNSCC) are two distinct types of aggressive head and neck cancers with early age onsets. Their recently identified genomic landscapes by whole-exome sequencing (WES) clearly reveal critical roles of: (1) inflammation via NF-kB activation, (2) survival via PI3K aberrations, and perhaps (3) immune evasion via MHC loss in these cancers as summarized in this review. Immediate outcomes of these WES studies include the identification of potential prognostic biomarkers, and druggable events for these cancers. The impact of these genomic findings on the development of precision medicine and immunotherapies will be discussed. For both of these cancers, the main lethality comes from metastases and disease recurrences which may represent therapy resistance. Thus, potential curing of these cancers still relies on future identification of key genomic drivers and likely druggable events in recurrent and metastatic forms of these intrinsically aggressive cancers of the head and neck.

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APOBEC-mediated genomic alterations link immunity and viral infection during human papillomavirus-driven cervical carcinogenesis

Cited by 17 publications

References 42 publications

APOBEC3B up-regulation independently predicts ovarian cancer prognosis: a cohort study

APOBEC3B up-regulation independently predicts ovarian cancer prognosis: a cohort study

The Role of Epstein–Barr Virus in Cervical Cancer: A Brief Update

Genomic Landscapes of EBV-Associated Nasopharyngeal Carcinoma vs. HPV-Associated Head and Neck Cancer

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