The role and regulation of Maf proteins in cancer

Deng, Ying; Lu, Liqing; Zhang, Huajun; Fu, Ying; Liu, Ting; Chen, Yongheng

doi:10.1186/s40364-023-00457-w

Cited by 15 publications

(11 citation statements)

References 213 publications

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“…The MAF family is classified into two subfamilies, per their protein size. One is the large MAF isoforms (lMAFs), including MAFA, MAFB, c-MAF, and NRL, which are characterised by the presence of an activation domain at the N-terminal [ 12 ]. lMAFs are about 240–340 amino acids in length.…”

Section: Nrf2 Signalling In Stress and Diseasesmentioning

confidence: 99%

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The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

Zhang

Zeng

et al. 2023

Biomedicines

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Age-related diseases, such as Parkinson’s disease, Alzheimer’s disease, cardiovascular diseases, cancers, and age-related macular disease, have become increasingly prominent as the population ages. Oxygen is essential for living organisms, but it may also cause disease when it is transformed into reactive oxygen species via biological processes in cells. Most of the production of ROS occurs in mitochondrial complexes I and III. The accumulation of ROS in cells causes oxidative stress, which plays a crucial role in human ageing and many diseases. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key antioxidant transcription factor that plays a central role in many diseases and ageing in general. It regulates many downstream antioxidative enzymes when cells are exposed to oxidative stress. A basic-region leucine zipper (bZIP) transcription factor, MAF, specifically the small MAF subfamily (sMAFs), forms heterodimers with Nrf2, which bind with Maf-recognition elements (MAREs) in response to oxidative stress. The role of this complex in the human retina remains unclear. This review summarises the current knowledge about Nrf2 and its downstream signalling, especially its cofactor—MAF, in ageing and diseases, with a focus on the retina. Since Nrf2 is the master regulator of redox homeostasis in cells, we hypothesise that targeting Nrf2 is a promising therapeutic approach for many age-related diseases.

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Section: Nrf2 Signalling In Stress and Diseasesmentioning

confidence: 99%

“…lMAFs are about 240–340 amino acids in length. The other subfamily is sMAFs, including MAFF, MAFG, and MAFK, which are featured as 150–160 amino acids without activation domains [ 12 ].…”

Section: Nrf2 Signalling In Stress and Diseasesmentioning

confidence: 99%

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

Zhang

Zeng

et al. 2023

Biomedicines

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“…This observation gains significance due to the intricate and context-dependent interplay between MAFB and VEGF signalling in the realm of cancer biology. MAFB, has previously been shown to critically contribute to various cellular processes, encompassing differentiation, proliferation, and metastasis(47–49). This study reveals an intriguing potential for crosstalk between MAFB and VEGF signalling pathways which is particularly interesting in light of recent studies demonstrating the activation of MAFB by VEGFR-3.…”

Section: Discussionmentioning

confidence: 99%

Integrating single-cell transcriptomics with Artificial Intelligence reveals pan-cancer biomarkers of brain metastasis

Lusby,

Carl,

Tiwari

2024

Preprint

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Brain metastasis (BrM) represents a devastating complication across various cancer types, posing as a significant contributor to global morbidity and mortality. Hence, identifying robust biomarkers for early detection across various cancer types with a propensity for BrMs and their therapeutic targeting is highly timely and critical. In this study, we leveraged single-cell RNA sequencing (scRNA-seq) data from six cancer types and combined with convolutional neural network (CNN)-based ScaiVision algorithm to identify a pan-cancer BrM signature that achieved remarkable accuracy in distinguishing BrM from primary tumour cells. Further analysis revealed that the BrM signature was not only prognostic but also detectable in bulk RNA-seq data, providing a stratification tool for patients with high or low metastatic potential. Strikingly, this signature was detected at high levels in the tumour educated platelets, showcasing its potential as a minimally invasive tool for metastasis detection. High BrM signature scores were associated with reduced patient survival, particularly in cancers prone to brain metastasis, such as renal and colorectal cancers. Further analysis uncovered VEGF signalling as a central driver of communication networks in high BrM-scored cells. Accordingly, drug repurposing analysis identified Pazopanib as a candidate for targeting highly metastatic cells that disrupts VEGF signalling networks, and potentially impedes brain metastatic progression in multiple cancer types. This study presents a comprehensive pan-cancer BrM signature with clinical implications for early detection and therapeutic intervention in brain metastasis.

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“…The Maf proteins (Mafs) belong to the activator protein-1 (AP-1) superfamily and are basic leucine zipper transcription factors. MafG, MafF and MafK belongs to small Mafs (approximately 150–160 amino acids) [ 41 ]. MafG accelerates cell proliferation and inhibits cell apoptosis in lung adenocarcinoma [ 42 ], while MafF promotes tumor invasion through heterodimerizing with Bach1 and activating the IL11/STAT3 pathway in breast cancer [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Integration of single-cell regulon atlas and multi-omics data for prognostic stratification and personalized treatment prediction in human lung adenocarcinoma

et al. 2023

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Transcriptional programs are often dysregulated in cancers. A comprehensive investigation of potential regulons is critical to the understanding of tumorigeneses. We first constructed the regulatory networks from single-cell RNA sequencing data in human lung adenocarcinoma (LUAD). We next introduce LPRI (Lung Cancer Prognostic Regulon Index), a precision oncology framework to identify new biomarkers associated with prognosis by leveraging the single cell regulon atlas and bulk RNA sequencing or microarray datasets. We confirmed that LPRI could be a robust biomarker to guide prognosis stratification across lung adenocarcinoma cohorts. Finally, a multi-omics data analysis to characterize molecular alterations associated with LPRI was performed from The Cancer Genome Atlas (TCGA) dataset. Our study provides a comprehensive chart of regulons in LUAD. Additionally, LPRI will be used to help prognostic prediction and developing personalized treatment for future studies.

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The role and regulation of Maf proteins in cancer

Cited by 15 publications

References 213 publications

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

Integrating single-cell transcriptomics with Artificial Intelligence reveals pan-cancer biomarkers of brain metastasis

Integration of single-cell regulon atlas and multi-omics data for prognostic stratification and personalized treatment prediction in human lung adenocarcinoma

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