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Clinical & Translational Oncology :... Jan 2024The MAF bZIP transcription factor G-antisense RNA 1 (MAFG-AS1) is located on chromosome 17. MAFG-AS1 was upregulated in 15 human cancers. MAFG-AS1 not only suppresses 16... (Review)
Review
The MAF bZIP transcription factor G-antisense RNA 1 (MAFG-AS1) is located on chromosome 17. MAFG-AS1 was upregulated in 15 human cancers. MAFG-AS1 not only suppresses 16 miRNAs but also directly impacts 22 protein-coding genes' expression. Notably, abnormal MAFG-AS1 expression is connected to clinicopathological characteristics and a worse prognosis in a variety of cancers. Moreover, MAFG-AS1 takes its part in the tumorigenesis and progression of various human malignancies by suppressing apoptosis and promoting proliferation, migration, invasion, aerobic glycolysis, ferroptosis, angiogenesis, EMT, and metastasis. Besides, it can predict treatment effectiveness in ER + breast cancer, urothelial bladder carcinoma, and liver cancer by functioning as a trigger of resistance to tamoxifen, sorafenib, and cisplatin. This study systematically presents the functions of MAFG-AS1 in various cancers, as well as the findings of bioinformatics analyses of the MAFG-AS1, which should give clear advice for future research.
Topics: Humans; Female; Carcinogens; MicroRNAs; RNA, Antisense; Liver Neoplasms; Breast Neoplasms; Cell Transformation, Neoplastic; RNA, Long Noncoding; Cell Proliferation; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Cell Movement; Repressor Proteins; MafG Transcription Factor
PubMed: 37351806
DOI: 10.1007/s12094-023-03246-x -
Internal Medicine (Tokyo, Japan) Jan 2023The increasing number of patients with chronic kidney disease (CKD) is being recognized as an emerging global health problem. Recently, it has become clear that injury... (Review)
Review
The increasing number of patients with chronic kidney disease (CKD) is being recognized as an emerging global health problem. Recently, it has become clear that injury and loss of glomerular visceral epithelial cells, known as podocytes, is a common early event in many forms of CKD. Podocytes are highly specialized epithelial cells that cover the outer layer of the glomerular basement membrane. They serve as the final barrier to urinary protein loss through the formation and maintenance of specialized foot-processes and an interposed slit-diaphragm. We previously reported that the transcription factor MafB regulates the podocyte slit diaphragm protein production and transcription factor Tcf21. We showed that the forced expression of MafB was able to prevent CKD. In this review, we discuss recent advances and offer an updated overview of the functions of podocyte-specific transcription factors in kidney biology, aiming to present new perspectives on the progression of CKD and respective therapeutic strategies.
Topics: Humans; Podocytes; Transcription Factors; Glomerular Basement Membrane; Epithelial Cells; Renal Insufficiency, Chronic; Basic Helix-Loop-Helix Transcription Factors; MafB Transcription Factor
PubMed: 35249929
DOI: 10.2169/internalmedicine.9336-22 -
ELife May 2020() and transcription factors (TFs) have compensatory roles in repressing somatostatin (SST) interneuron (IN) production in medial ganglionic eminence (MGE) secondary...
() and transcription factors (TFs) have compensatory roles in repressing somatostatin (SST) interneuron (IN) production in medial ganglionic eminence (MGE) secondary progenitors in mice. and conditional deletion (cDKO) decreases the survival of MGE-derived cortical interneurons (CINs) and changes their physiological properties. Herein, we show that (1) and are positively regulated by and to drive IN morphological maturation; (2) and promote expression which specifies parvalbumin (PV) INs; (3) , and are candidate markers of immature PV hippocampal INs (HIN). Furthermore, / neonatal cDKOs have decreased CINs and increased HINs, that express , an HIN specific marker. Our findings not only elucidate key gene targets of and that control IN development, but also identify for the first time TFs that differentially regulate CIN vs. HIN production.
Topics: Animals; Female; Gene Expression Regulation; Interneurons; MEF2 Transcription Factors; MafB Transcription Factor; Mice; Nervous System Diseases; Pregnancy; Protein Precursors; Proto-Oncogene Proteins c-maf; Receptors, CXCR4; Receptors, Opioid; Single-Cell Analysis; Synaptosomal-Associated Protein 25; Transcriptome
PubMed: 32452758
DOI: 10.7554/eLife.54903 -
Pathology, Research and Practice Mar 2023Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. At the same time, they can regulate various biological functions and therefore... (Review)
Review
Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. At the same time, they can regulate various biological functions and therefore play an essential role as oncogenes or tumor suppressors in human cancers. MAFG-AS1 is an antisense RNA of MAF BZIP Transcription Factor G (MAFG) located at chromosome 17q25.3 head-to-head with the MAFG encoding gene containing a transcript size of 1895 bp. Accumulating evidence shows that MAFG-AS1 is overexpressed in many cancers, functions as an oncogene, and is significantly associated with poor clinical characteristics and prognosis. In this review, we first discuss the recent literature regarding the role of MAFG-AS1 in different cancers as well as its diagnostic and prognostic values. Then we will provide insights into its biological functions, such as its role in cancer progression, competing endogenous RNA (ceRNA) activity, regulation of EMT, glycolysis, energy metabolism, transcription factors, proteasomal degradation, and signaling pathways.
Topics: Humans; Carcinogenesis; Cell Transformation, Neoplastic; Neoplasms; Oncogenes; RNA, Antisense; RNA, Long Noncoding; Gene Expression Regulation, Neoplastic; MicroRNAs; Cell Proliferation; Repressor Proteins; MafG Transcription Factor
PubMed: 36736142
DOI: 10.1016/j.prp.2023.154348 -
The Journal of Experimental Medicine Dec 2022The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type...
The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient transporters in the mid-villus region. Functionally, enterocytes required c-Maf to appropriately differentiate along the villus axis. Specifically, gene programs controlling carbohydrate and protein absorption were c-Maf-dependent. Consequently, epithelial cell-specific c-Maf deletion resulted in impaired enterocyte maturation and nutrient uptake, including defects in the adaptation to different nutrient availability. Concomitantly, intraepithelial lymphocytes were less abundant, while commensal epithelial cell-attaching SFB overgrew in a c-Maf-deficient environment, highlighting the close interdependence between the intestinal epithelium, immune system, and microbiota. Collectively, our data identified c-Maf as a key regulator of SI enterocyte differentiation and function, essential for nutrient, immune, and microbial homeostasis.
Topics: Animals; Carbohydrates; Enterocytes; Intestines; Mice; Nutrients; Proto-Oncogene Proteins c-maf; Transcription Factors
PubMed: 36121416
DOI: 10.1084/jem.20220233 -
Biomolecules Jul 2021MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed...
MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell carcinoma) cell lines. In this study, we shed further light on the interaction between miR-1290 and , as well as on cellular MAF protein localization in LSCC. We confirmed the direct interaction between miR-1290 and 3'UTR by a dual-luciferase reporter assay. In addition, we used immunohistochemistry staining to analyze MAF protein distribution and observed loss of MAF nuclear expression in 58% LSCC samples, of which 10% showed complete absence of MAF, compared to nuclear and cytoplasmatic expression in 100% normal mucosa. Using TCGA data, bisulfite pyrosequencing and CNV analysis, we excluded the possibility that loss-of-function mutations, promoter region DNA methylation or CNV are responsible for MAF loss in LSCC. Finally, we identified genes involved in the regulation of apoptosis harboring the MAF binding motif in their promoter region by applied FIMO and DAVID GO analysis. Our results highlight the role of miR-1290 in suppressing MAF expression in LSCC. Furthermore, MAF loss or mislocalization in FFPE LSCC tumor samples might suggest that MAF acts as a LSCC tumor suppressor by regulating apoptosis.
Topics: 3' Untranslated Regions; Aged; Cell Line, Tumor; Cell Nucleus; DNA Methylation; Female; Gene Dosage; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Male; MicroRNAs; Middle Aged; Mutation; Promoter Regions, Genetic; Proto-Oncogene Proteins c-maf; Squamous Cell Carcinoma of Head and Neck
PubMed: 34356658
DOI: 10.3390/biom11071035 -
Cell Reports Apr 2023Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular...
Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular regulation of myofiber type is not entirely understood; particularly, information on regulators of fast-twitch muscle is scarce. Here, we demonstrate that the large Maf transcription factor family dictates fast type IIb myofiber specification in mice. Remarkably, the ablation of three large Mafs leads to the drastic loss of type IIb myofibers, resulting in enhanced endurance capacity and the reduction of muscle force. Conversely, the overexpression of each large Maf in the type I soleus muscle induces type IIb myofibers. Mechanistically, a large Maf directly binds to the Maf recognition element on the promoter of myosin heavy chain 4, which encodes the type IIb myosin heavy chain, driving its expression. This work identifies the large Maf transcription factor family as a major regulator for fast type IIb muscle determination.
Topics: Mice; Animals; Myosin Heavy Chains; Muscle Fibers, Fast-Twitch; Muscle, Skeletal; Maf Transcription Factors, Large; Proto-Oncogene Proteins c-maf
PubMed: 36952339
DOI: 10.1016/j.celrep.2023.112289 -
Clinical and Translational Medicine Mar 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves T follicular helper (T ) cell-mediated humoral immune responses. Absent in melanoma 2...
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves T follicular helper (T ) cell-mediated humoral immune responses. Absent in melanoma 2 (human AIM2 and murine Aim2) is a well-known component of the inflammasome in the innate immune system. Surprisingly, we observed that in SLE patients, upregulated levels of AIM2 expression were found in peripheral blood and skin lesions, with the highest levels detected in T -like cells. In the CD4 Aim2 conditional knockout mice, a markedly reduced T cell response was observed, with significantly lower levels of serum autoantibodies and proteinuria, as well as profoundly reduced renal IgG deposition in pristane-induced lupus mice. Mechanistically, IL-21 was found to recruit hydroxymethyltransferase ten-eleven translocation 2 (TET2) to the AIM2 promoter, resulting in DNA demethylation and increased transcription of AIM2. In addition, AIM2 could regulate c-MAF expression to enhance IL-21 production, which consequently promoted T cell differentiation. Our results have identified a role of AIM2 in promoting the T cell response and further revealed that the IL-21-TET2-AIM2-c-MAF signalling pathway is dysregulated in lupus pathogenesis, which provides a potential therapeutic target for SLE.
Topics: Animals; DNA-Binding Proteins; Dioxygenases; Humans; Interleukins; Lupus Erythematosus, Systemic; Mice; Proto-Oncogene Proteins c-maf; T Follicular Helper Cells
PubMed: 35343082
DOI: 10.1002/ctm2.781 -
Frontiers in Immunology 2020Defective IFN production and exacerbated inflammatory and pro-fibrotic responses are hallmarks of SARS-CoV-2 infection in severe COVID-19. Based on these hallmarks, and...
Defective IFN production and exacerbated inflammatory and pro-fibrotic responses are hallmarks of SARS-CoV-2 infection in severe COVID-19. Based on these hallmarks, and considering the pivotal role of macrophages in COVID-19 pathogenesis, we hypothesize that the transcription factors MAFB and MAF critically contribute to COVID-19 progression by shaping the response of macrophages to SARS-CoV-2. Our proposal stems from the recent identification of pathogenic lung macrophage subsets in severe COVID-19, and takes into consideration the previously reported ability of MAFB to dampen IFN type I production, as well as the critical role of MAFB and MAF in the acquisition and maintenance of the transcriptional signature of M-CSF-conditioned human macrophages. Solid evidences are presented that link overexpression of MAFB and silencing of MAF expression with clinical and biological features of severe COVID-19. As a whole, we propose that a high MAFB/MAF expression ratio in lung macrophages could serve as an accurate diagnostic tool for COVID-19 progression. Indeed, reversing the macrophage MAFB/MAF expression ratio might impair the exacerbated inflammatory and profibrotic responses, and restore the defective IFN type I production, thus becoming a potential strategy to limit severity of COVID-19.
Topics: COVID-19; Gene Expression Profiling; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Macrophages; Maf Transcription Factors; MafB Transcription Factor; SARS-CoV-2; Severity of Illness Index
PubMed: 33312178
DOI: 10.3389/fimmu.2020.603507 -
JNCI Cancer Spectrum Aug 2021The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a nonamplified gene in the primary tumor and benefit from adjuvant ZA.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a nonamplified gene in the primary tumor and benefit from adjuvant ZA. Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study.
METHODS
A retrospective analysis of gene status in NSABP B-34 was performed. Eligible patients were randomly assigned to standard adjuvant systemic treatment plus 3 years oral clodronate (1600 mg/daily) or placebo. Tumors were tested for gene amplification and analyzed for their relationship to clodronate for disease-free survival (DFS) and overall survival (OS) in nonamplified patients. All statistical tests were 2-sided .
RESULTS
status was assessed in 2533 available primary tumor samples from 3311 patients. Of these, 37 withdrew consent; in 77 samples, no tumor was found; 536 assays did not meet quality standards, leaving 1883 (77.8%) evaluable for assay by fluorescence in situ hybridization (947 from placebo and 936 from clodronate arms). At 5 years, in nonamplified patients receiving clodronate, DFS improved by 30% (hazard ratio = 0.70, 95% confidence interval = 0.51 to 0.94; =.02). OS improved at 5 years (hazard ratio = 0.59, 95% confidence interval = 0.37 to 0.93; =.02) remaining statistically significant for clodronate throughout study follow-up. Conversely, adjuvant clodronate in women with -amplified tumors was not associated with benefit but rather possible harm in some subgroups. Association between MAF status and menopausal status was not seen.
CONCLUSIONS
Nonamplified showed statistically significant benefits (DFS and OS) with oral clodronate, supporting validation of the AZURE study.
Topics: Administration, Oral; Bone Density Conservation Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Clodronic Acid; Confidence Intervals; Disease-Free Survival; Double-Blind Method; Female; Gene Amplification; Humans; In Situ Hybridization, Fluorescence; Injections, Intravenous; Middle Aged; Placebos; Proto-Oncogene Proteins c-maf; Retrospective Studies; Zoledronic Acid
PubMed: 34377934
DOI: 10.1093/jncics/pkab054