Apolipoprotein B <scp>mRNA</scp> editing enzyme catalytic polypeptide‐like family genes activation and regulation during tumorigenesis

Gao, Jianlong; Choudhry, Hani; Cao, Wei

doi:10.1111/cas.13658

Cited by 22 publications

(19 citation statements)

References 66 publications

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“…Proteins E6 and E7 from HR-HPV types are oncogenes that are important for carcinogenesis and have some key activities such as the induction of replication stress, host DNA repair responses and downregulation of the pRB and p53 tumour suppressors [ 204 ] that may serve to trigger the mutagenic activity of A3 proteins seen in HPV-associated cancers ( figure 6 ). Several studies indicate that NF-κB pathway activation, p53 inactivation by HPV oncoprotein E6 activation, or loss-of-function mutations in the TP53 gene and replication stress activation are responsible for transcriptional activation of APOBEC, in particular, A3B ( figure 6 ) [ 95 , 149 , 205 , 206 ]. Both the E6 and E7 proteins from HPV16 can act independently to increase A3B expression in immortalized keratinocytes through this pathway; E6 via p53 degradation, with E7 likely acting through its effects on the p107 and p130 pRb family pocket proteins in the DREAM (DP1, RB-like, E2F4 and MuvB) complex [ 150 ], thus also offering a mechanistic basis for the E7-mediated A3B upregulation previously described ( figure 6 ) [ 207 ].…”

Section: A3 Enzymes and Cancermentioning

confidence: 99%

The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead

2020

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Cancer is considered a group of diseases characterized by uncontrolled growth and spread of abnormal cells and is propelled by somatic mutations. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of enzymes are endogenous sources of somatic mutations found in multiple human cancers. While these enzymes normally act as an intrinsic immune defence against viruses, they can also catalyse ‘off-target’ cytidine deamination in genomic single-stranded DNA intermediates. The deamination of cytosine forms uracil, which is promutagenic in DNA. Key factors to trigger the APOBEC ‘off-target’ activity are overexpression in a non-normal cell type, nuclear localization and replication stress. The resulting uracil-induced mutations contribute to genomic variation, which may result in neutral, beneficial or harmful consequences for the cancer. This review summarizes the functional and biochemical basis of the APOBEC3 enzyme activity and highlights their relationship with the most well-studied cancers in this particular context such as breast, lung, bladder, and human papillomavirus-associated cancers. We focus on APOBEC3A, APOBEC3B and APOBEC3H haplotype I because they are the leading candidates as sources of somatic mutations in these and other cancers. Also, we discuss the prognostic value of the APOBEC3 expression in drug resistance and response to therapies.

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Section: A3 Enzymes and Cancermentioning

confidence: 99%

The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead

2020

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“…A3 proteins were originally identified as factors of the innate immunity due to their mutagenic activity on viral genomes, and have recently joined the growing list of key intrinsic mutagens that play a part in oncogenesis [1]. Evidence for A3 mutagenicity consists of the presence of their mutational signature in cancer genomes [2], the effects observed when overexpressed in tumor tissues [3,4], as well as the correlation of APOBEC signature mutations with poor prognosis [5,6]. Nevertheless, the precise biology of each APOBEC3 protein in cancer cells remains unknown.…”

Section: Introductionmentioning

confidence: 99%

APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression

et al. 2020

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Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminase 3B (A3B) is a DNA editing enzyme which induces genomic DNA mutations in multiple myeloma and in various other cancers. APOBEC family proteins are highly homologous so it is especially difficult to investigate the biology of specifically A3B in cancer cells. To easily and comprehensively investigate A3B function in myeloma cells, we used CRISPR/Cas9 to generate A3B reporter cells that contain 3×FLAG tag and IRES-EGFP sequences integrated at the end of the A3B gene. These reporter cells stably express 3xFLAG tagged A3B and the reporter EGFP and this expression is enhanced by known stimuli, such as PMA. Conversely, shRNA knockdown of A3B decreased EGFP fluorescence and 3xFLAG tagged A3B protein levels. We screened a series of anticancer treatments using these cell lines and identified that most conventional therapies, such as antimetabolites or radiation, exacerbated endogenous A3B expression, but recent molecular targeted therapeutics, including bortezomib, lenalidomide and elotuzumab, did not. Furthermore, chemical inhibition of ATM, ATR and DNA-PK suppressed EGFP expression upon treatment with antimetabolites. These results suggest that DNA damage triggers A3B expression through ATM, ATR and DNA-PK signaling.

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“…APOA1 could promote the increase of macrophage infiltration, decrease TMB and metastasis, and improve the survival rate, similar to its effects in colorectal cancer [ 25 , 26 ]. APOB caused a high mutation burden of cancer genes and tumorigenesis [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma

Zhao

Fu²,

Han

et al. 2021

Cancer Cell Int

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Background UCEC is the most common gynecological malignancy in many countries, and its mechanism of occurrence and development is related to tumor mutation burden (TMB) and immune cell infiltration. Therefore, it is necessary to systematically explore the TMB-related gene profile in immune cells to improve the prognosis of UCEC. Methods We integrated TMB-related genes with basic clinical information of UCEC patients based on TCGA dataset. Differentially expressed genes (DEGs) were selected through differential expression screening, PPI, and enrichment analysis. Additionally, we analyzed the components of immune cell infiltration of the DEGs to obtain the differential immunity-related genes. A single factor and multifactor Cox regression analyses were conducted to establish new prognostic indicators of OS and DFS based on TMB-related immune genes. To further study the correlation between survival and immune cell infiltration, a Cox model based on these immune infiltration compositions was built. Using the clinical variables, we established nomograms for OS and DFS. Results 393 DEGs were significantly associated with clinical outcomes and the immune component in patients with UCEC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and protein-protein interaction network (PPI) analyses revealed the role of these genes and information on related pathways. Then, two prognostic models were established based on the differential immune genes for OS (GFAP and MX2) and DFS (MX2, GFAP, IGHM, FGF20, and TRAV21). In DFS, the differential immune genes were related to CD4+ T cell, CD8+ T cell, macrophage, and neutrophil (all P < 0.05). B cell and CD8+ T cell were independent prognostic factors from among the immune cell elements in UCEC. Finally, the risk scores of these models were combined with the clinical elements-based nomogram models, and the AUC values were all over 0.7. Conclusions Our results identified several clinically significant differential immune genes and established relevant prognostic models, providing a basis for the molecular analysis of TMB and immune cells in UCEC, and identified potential prognostic and immune-related genes for UCEC. We added clinical related conditions for further analysis to confirm the identity of the genes and clinical elements-based models.

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Apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like family genes activation and regulation during tumorigenesis

Cited by 22 publications

References 66 publications

The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead

The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead

APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression

Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma

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