DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors

Felix, Fernanda Aragão; Silva, Leorik Pereira da; Lopes, Maria Luiza Diniz de Sousa; Sobral, Ana Paula Veras; Freitas, Roseana de Almeida; Souza, Lélia Batista de; Barboza, Carlos Augusto Galvão

doi:10.1016/j.archoralbio.2020.104987

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…APE1 was also upregulated in salivary gland carcinomas, and its levels increased depending on the malignant transformation process of the tumor [127]. APE1 overexpression was higher in smaller tumors displaying lymph node metastasis and invasive growth [127,128]. APE1 localization was mainly nuclear in every salivary gland tumor subtype analysed, except for adenoid cystic carcinomas, in which it was highlighted to present both nuclear and cytoplasmic localization [127,128].…”

mentioning

confidence: 93%

“…[ [38][39][40][41][42][43][44] Breast cancer Mainly nuclear staining, with nuclear and cytosolic staining in some malignant forms. [127,128] In bladder cancer (BCa), several studies detected high expression levels of the APE1 protein in tumor tissues, compared to normal adjacent tissues, that were associated with poor outcomes [39,41,44]. APE1 overexpression was also linked to lymphovascular invasion features, as high VEGFA levels and an infiltration of CD163 + tumor-associated macrophages (TAMs) [42].…”

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confidence: 99%

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Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons

Malfatti,

Bellina,

Antoniali

et al. 2023

Cells

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APE1 is an essential endodeoxyribonuclease of the base excision repair pathway that maintains genome stability. It was identified as a pivotal factor favoring tumor progression and chemoresistance through the control of gene expression by a redox-based mechanism. APE1 is overexpressed and serum-secreted in different cancers, representing a prognostic and predictive factor and a promising non-invasive biomarker. Strategies directly targeting APE1 functions led to the identification of inhibitors showing potential therapeutic value, some of which are currently in clinical trials. Interestingly, evidence indicates novel roles of APE1 in RNA metabolism that are still not fully understood, including its activity in processing damaged RNA in chemoresistant phenotypes, regulating onco-miRNA maturation, and oxidized RNA decay. Recent data point out a control role for APE1 in the expression and sorting of onco-miRNAs within secreted extracellular vesicles. This review is focused on giving a portrait of the pros and cons of the last two decades of research aiming at the identification of inhibitors of the redox or DNA-repair functions of APE1 for the definition of novel targeted therapies for cancer. We will discuss the new perspectives in cancer therapy emerging from the unexpected finding of the APE1 role in miRNA processing for personalized therapy.

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confidence: 93%

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confidence: 99%

Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons

Malfatti,

Bellina,

Antoniali

et al. 2023

Cells

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“…Although there is a lack of data in general exploring the role of DDR pathways in salivary gland malignancies [ 96 ], DDR genes have been recently implicated in ACC pathogenesis. Ho et al demonstrated that 27% of ACC patients demonstrated altered expression of DDR/checkpoint signalling genes, including TP53 , UHRF1 , ATM and BRCA1 [ 12 ].…”

Section: Dna Damage Repair Gene (Ddrg) Mutationsmentioning

confidence: 99%

“…Felix et al examined the mutational profile of DDR genes in salivary gland ACC pathogenesis and noted high expression levels of a nucleotide excision repair gene XPF in minor salivary gland ACC samples [ 96 ]. Furthermore, the APE1 protein that acts as a redox transcription factor coactivator and is involved in the base excision repair pathway was expressed in the nucleus/cytoplasm of 50% of ACC cases.…”

Section: Dna Damage Repair Gene (Ddrg) Mutationsmentioning

confidence: 99%

A Review of the Molecular Landscape of Adenoid Cystic Carcinoma of the Lacrimal Gland

Powell,

Kulakova,

Kennedy

2023

IJMS

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Adenoid cystic carcinoma (ACC) has a worldwide incidence of three to four cases per million population. Although more cases occur in the minor and major salivary glands, it is the most common lacrimal gland malignancy. ACC has a low-grade, indolent histological appearance, but is relentlessly progressive over time and has a strong proclivity to recur and/or metastasise. Current treatment options are limited to complete surgical excision and adjuvant radiotherapy. Intra-arterial systemic therapy is a recent innovation. Recurrent/metastatic disease is common due to perineural invasion, and it is largely untreatable as it is refractory to conventional chemotherapeutic agents. Given the rarity of this tumour, the molecular mechanisms that govern disease pathogenesis are poorly understood. There is an unmet, critical need to develop effective, personalised targeted therapies for the treatment of ACC in order to reduce morbidity and mortality associated with the disease. This review details the evidence relating to the molecular underpinnings of ACC of the lacrimal gland, including the MYB–NFIB chromosomal translocations, Notch-signalling pathway aberrations, DNA damage repair gene mutations and epigenetic modifications.

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“…[ 13 , 14 , 15 , 16 ] For example, APEX1 and XRCC1 have been shown to participate in damage recognition and base repair at the site of the DNA damage. [ 17 ] Based on the important functions of both circRNAs and DNA damage, we speculated that circRNAs play a role in regulating DNA damage during the development of Cd‐induced lung cancer. Here, we constructed a chronic Cd‐induced malignant transformation model in mouse lungs and bronchial epithelial cell lines, and found that circRNA expression profiles changed significantly.…”

Section: Introductionmentioning

confidence: 99%

circCIMT Silencing Promotes Cadmium‐Induced Malignant Transformation of Lung Epithelial Cells Through the DNA Base Excision Repair Pathway

Chen

Cui

et al. 2023

Advanced Science

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Changes in gene expression in lung epithelial cells are detected in cancer tissues during exposure to pollutants, highlighting the importance of gene‐environmental interactions in disease. Here, a Cd‐induced malignant transformation model in mouse lungs and bronchial epithelial cell lines is constructed, and differences in the expression of non‐coding circRNAs are analyzed. The migratory and invasive abilities of Cd‐transformed cells are suppressed by circCIMT. A significant DNA damage response is observed after exposure to Cd, which increased further following circCIMT‐interference. It is found that APEX1 is significantly down‐regulated following Cd exposure. Furthermore, it is demonstrated that circCIMT bound to APEX1 during Cd exposure to mediate the DNA base excision repair (BER) pathway, thereby reducing DNA damage. In addition, simultaneous knockdown of both circCIMT and APEX1 promotes the expression of cancer‐related genes and malignant transformation after long‐term Cd exposure. Overall, these findings emphasis the importance of genetic‐epigenetic interactions in chemical‐induced cancer transformation.

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DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors

Cited by 5 publications

References 36 publications

Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons

Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons

A Review of the Molecular Landscape of Adenoid Cystic Carcinoma of the Lacrimal Gland

circCIMT Silencing Promotes Cadmium‐Induced Malignant Transformation of Lung Epithelial Cells Through the DNA Base Excision Repair Pathway

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