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1.
Clin Transl Oncol ; 26(1): 52-68, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37351806

RESUMO

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.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Carcinógenos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Antissenso/genética , Neoplasias Hepáticas/genética , Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas Repressoras/genética , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo
2.
Eur J Med Res ; 28(1): 497, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37941063

RESUMO

Long noncoding RNAs (lncRNAs) refer to a type of non-protein-coding transcript of more than 200 nucleotides. LncRNAs play fundamental roles in disease development and progression, and lncRNAs are dysregulated in many pathophysiological processes. Thus, lncRNAs may have potential value in clinical applications. The lncRNA, MAF BZIP Transcription Factor G (MAFG)-AS1, is dysregulated in several cancer, including breast cancer, lung cancer, liver cancer, bladder cancer, colorectal cancer, gastric cancer, esophagus cancer, prostate cancer, pancreatic cancer, ovarian cancer, and glioma. Altered MAFG-AS1 levels are also associated with diverse clinical characteristics and patient outcomes. Mechanistically, MAFG-AS1 mediates a variety of cellular processes via the regulation of target gene expression. Therefore, the diagnostic, prognostic, and therapeutic aspects of MAFG-AS1 have been widely explored. In this review, we discuss the expression, major roles, and molecular mechanisms of MAFG-AS1, the relationship between MAFG-AS1 and clinical features of diseases, and the clinical applications of MAFG-AS1.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , Neoplasias Pulmonares/genética , Neoplasias da Mama/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral , Proteínas Repressoras/genética , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo
3.
Growth Factors ; 41(3): 152-164, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37428861

RESUMO

We investigated the mechanism of ETS-translocation variant 1 (ETV1)/lncRNA-MAFG-AS1 in pancreatic cancer (PC). MAFG-AS1 and ETV1 levels in PC cell lines and HPNE cells were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB). After transfection with sh-MAFG-AS1, PC cell invasion, migration, proliferation, and epithelial-mesenchymal transition (EMT)-related proteins were measured by 5-ethynyl-2'-deoxyuridine (EdU), Transwell assay, and WB. The binding between ETV1 and MAFG-AS1 was studied using dual-luciferase assay and chromatin immunoprecipitation. The interactions between MAFG-AS1, IGF2BP2, and ETV1 were tested. Combined experiments were further performed using sh-MAFG-AS1 and pcDNA-ETV1 simultaneously. ETV1/MAFG-AS1 was highly expressed in PC cells. Blocking MAFG-AS1 inhibited the malignant behaviors of PC cells. ETV1 induced MAFG-AS1 transcription in PC cells. MAFG-AS1 stabilized ETV1 mRNA by recruiting IGF2BP2. ETV1 overexpression partially antagonized the suppression of silencing MAFG-AS1 on PC cells. ETV1-induced MAFG-AS1 stabilized the ETV1 expression by recruiting IGF2BP2 and promoted PC cell migration, invasion, proliferation, and EMT.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/genética , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias Pancreáticas
4.
J Med Chem ; 66(9): 6184-6192, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37097833

RESUMO

Nuclear factor erythroid-related 2-factor 2 (Nrf2) is a transcription factor traditionally thought of as a cellular protector. However, in many cancers, Nrf2 is constitutively activated and correlated with therapeutic resistance. Nrf2 heterodimerizes with small musculoaponeurotic fibrosarcoma Maf (sMAF) transcription factors, allowing binding to the antioxidant responsive element (ARE) and induction of transcription of Nrf2 target genes. While transcription factors are historically challenging to target, stapled peptides have shown great promise for inhibiting these protein-protein interactions. Herein, we describe the first direct cell-permeable inhibitor of Nrf2/sMAF heterodimerization. N1S is a stapled peptide designed based on AlphaFold predictions of the interactions between Nrf2 and sMAF MafG. A cell-based reporter assay combined with in vitro biophysical assays demonstrates that N1S directly inhibits Nrf2/MafG heterodimerization. N1S treatment decreases the transcription of Nrf2-dependent genes and sensitizes Nrf2-dependent cancer cells to cisplatin. Overall, N1S is a promising lead for the sensitization of Nrf2-addicted cancers.


Assuntos
Fator 2 Relacionado a NF-E2 , Proteínas Repressoras , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo , Regulação da Expressão Gênica , Peptídeos/metabolismo
5.
Pathol Res Pract ; 243: 154348, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36736142

RESUMO

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.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Neoplasias/genética , Oncogenes , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Proliferação de Células/genética , Proteínas Repressoras/genética , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo
6.
Environ Sci Pollut Res Int ; 30(7): 19250-19258, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36229729

RESUMO

Recent references discovered that lncRNAs acted roles in malignant cancer development. However, the role of MAFG-AS1 in acute myeloid leukemia (AML) development remains unknown. MAFG-AS1 and miR-147b were determined in AML cells and specimens using qRT-PCR assay. Cell proliferation was detected by CCK-8 analysis and flow cytometry was carried out to measure cell cycle. Luciferase reporter analysis was done to determine the mechanism of MAFG-AS1 and miR-147b. We noted that MAFG-AS1 was overexpressed in AML cells and in serum and bone narrow from AML compared with normal controls specimen. Elevated expression of MAFG-AS1 increased cell growth, cycle and EMT in AML cell HL-60 cell. MAFG-AS1 sponged miR-147b expression in HL-60 cell. Moreover, miR-147b was downregulated in AML cells and in serum and bone narrow from AML compared with normal control specimen. miR-147b was negatively correlated with MAFG-AS1 in the serum and bone narrow of AML cases. We illustrated that HOXA9 was one target of miR-147b and ectopic expression of MAFG-AS1 enhanced HOXA9 expression HL-60 cell. Forced expression of MAFG-AS1 induced cell growth, cycle, and EMT via promoting HOXA9. These data illustrated that MAFG-AS1 acted as one oncogenic gene and accelerated AML progression via modulating miR-147b/HOXA9 axis.


Assuntos
Leucemia Mieloide Aguda , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Movimento Celular/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Proliferação de Células/genética , Linhagem Celular Tumoral , Proteínas Repressoras/genética , Fator de Transcrição MafG/genética
7.
Acta Neurobiol Exp (Wars) ; 82(3): 315-326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36214714

RESUMO

This study was designed to explore the function of lncRNA MAFG­AS1/miR­642a­5p/Notch1 in glioblastoma (GBM) cells under radiation. GBM cells (M059K and M059J) were transfected or/and irradiated. Western blotting was used to detect Notch1 protein and its downstream Hes1 protein. Cell Counting Kit-8 assay and flow cytometry were applied for viability and apoptosis tests, respectively. Luciferase reporter plasmids and Ago2 antibody were used to verify the predicted binding of miR­642a­5p to MAFG­AS1 or Notch1 mRNA. Notch1 and MAFG­AS1 were highly expressed and miR­642a­5p was lowly expressed in radioresistant M059K cells. Knockdown of Notch1 inhibited radioresistance and promoted apoptosis in M059K cells. MAFG­AS1 competed with Notch1 mRNA for binding of miR­642a­5p and therefore promoted the expression of Notch1. Overexpression of miR­642a­5p or silencing of MAFG­AS1 inhibited the radioresistance of M059K cells. Knockdown of Notch1 or overexpression of miR­642a­5p reduced viability and increased apoptosis in irradiated M059J cells overexpressing MAFG­AS1. MAFG­AS1 reduces the radiosensitivity of GBM cells via miR­642a­5p/Notch1 axis.


Assuntos
Glioblastoma , MicroRNAs , RNA Longo não Codificante , Receptor Notch1 , Linhagem Celular Tumoral , Proliferação de Células/genética , Glioblastoma/genética , Glioblastoma/radioterapia , Humanos , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro , Receptor Notch1/genética , Receptor Notch1/metabolismo , Proteínas Repressoras
8.
Biochem Biophys Res Commun ; 616: 95-103, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35653827

RESUMO

PURPOSE: We aimed to explore the function and competing endogenous RNA (ceRNA) pathway of MAFG-AS1 in breast cancer. METHODS: qRT-PCR assay identified the expression of MAFG-AS1, miR-3612 and FKBP4. We used Western blot analysis to test the autophagy related protein levels in breast cancer cells. Functional assays such as Cell Counting Kit-8 (CCK8) assay, BrdU proliferation assay, Caspase-3 activity detection were used to identify the function of MAFG-AS1, miR-3612 and FKBP4 in breast cancer cells. Mechanism assays were used to verify the interacting relationship among MAFG-AS1, miR-3612 and FKBP4, including RNA pull down assay, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. RESULTS: MAFG-AS1 and FKBP4 were both up-regulated in breast cancer tissues. MAFG-AS1 could function as an oncogene in breast cancer to activate cell proliferation, and inhibit cell apoptosis and autophagy. Meanwhile, MAFG-AS1 could sponge miR-3612 to elevate the expression of FKBP4. Besides, FKBP4 could activate the cell proliferation and inhibit cell apoptosis and autophagy, which could relieve the inhibitory effect of miR-3612 on breast cancer cells. CONCLUSION: MAFG-AS1 could activate breast cancer progression via modulating miR-3612/FKBP4 axis in vitro.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Proteínas de Ligação a Tacrolimo , Autofagia/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/genética , Progressão da Doença , Feminino , Humanos , Fator de Transcrição MafG/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/metabolismo
9.
Mol Biotechnol ; 64(9): 970-983, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35275356

RESUMO

Lung adenocarcinoma (LUAD) patients exhibit poor prognosis, primarily due to metastasis. Emerging studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in cancer progression and metastasis besides their physiological function. Here, we investigated the potential role of lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG-AS1) in LUAD metastasis by analyzing its expression in The Cancer Genome Atlas (TCGA) LUAD database, and its function in LUAD using in vitro and in vivo experiments. We performed bioinformatics analysis, western blotting, dual-luciferase reporter gene assay, RNA immunoprecipitation (RIP), and rescue assays to reveal the molecular mechanisms underlying MAFG-AS1 function. We observed augmented expression of MAFG-AS1 in LUAD tissues compared with normal adjacent tissues, and its association with poor prognosis. Furthermore, MAFG-AS1 overexpression promoted LUAD cell migration, proliferation, invasion, and epithelial mesenchymal transition (EMT). Besides, MAFG-AS1 also targeted miR-3196 directly by acting as an endogenous sponge, thereby rescuing the inhibition of SOX12, a target of miR-3196. Thus, the rescue assays demonstrated that MAFG-AS1 promotes cell migration, invasion, and EMT by modulating the miR-3196/SOX12 pathway. In conclusion, our findings suggest that MAFG-AS1/miR-3196/SOX12 axis regulates LUAD progression and is a potential therapeutic target for LUAD.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Adenocarcinoma/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo
10.
Mol Cell Biol ; 42(3): e0052021, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35129372

RESUMO

Members of the cap'n'collar (CNC) family of transcription factors, including Nrf1 and Nrf2, heterodimerize with small Maf (sMaf) proteins (MafF, MafG, and MafK) and regulate target gene expression through CNC-sMaf-binding elements (CsMBEs). We recently developed a unique tethered dimer assessment system combined with small Maf triple-knockout fibroblasts, which enabled the characterization of specific CNC-sMaf heterodimer functions. In this study, we evaluated the molecular function of the tethered Nrf1-MafG (T-N1G) heterodimer. We found that T-N1G activates the expression of proteasome subunit genes, well-known Nrf1 target genes, and binds specifically to CsMBEs in the proximity of these genes. T-N1G was also found to activate genes involved in proteostasis-related pathways, including endoplasmic reticulum-associated degradation, chaperone, and ubiquitin-mediated degradation pathways, indicating that the Nrf1-MafG heterodimer regulates a wide range of proteostatic stress response genes. By taking advantage of this assessment system, we found that Nrf1 has the potential to activate canonical Nrf2 target cytoprotective genes when strongly induced. Our results also revealed that transposable SINE B2 repeats harbor CsMBEs with high frequency and contribute to the target gene diversity of CNC-sMaf transcription factors.


Assuntos
Fator de Transcrição MafG , Fator 2 Relacionado a NF-E2 , Degradação Associada com o Retículo Endoplasmático , Fator de Transcrição MafG/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 1 Nuclear Respiratório/genética , Fator 1 Nuclear Respiratório/metabolismo , Proteínas Repressoras/metabolismo
11.
Cancer Gene Ther ; 29(3-4): 277-291, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34035482

RESUMO

Long non-coding RNAs (lncRNAs) were recently recognized to vitally function in a variety of cancer cellular events, including epithelial-mesenchymal transition (EMT), invasion, and migration, particularly in ovarian cancer (OC). Herein, we sought to investigate the potential role of MAFG-AS1 in the malignant behaviors of OC cells. The binding affinity between MAFG-AS1, miR-339-5p, NFKB1 or IGF1 was characterized so as to identify the underlying mechanism of corresponding their interactions. We conducted MAFG-AS1 overexpression or knockdown along with NFKB1 and IGF1 silencing to examine their effects on the EMT, migration, and invasion of OC cells. Tumors were xenografted in nude mice to validate the in vitro findings. Our data showed significantly high expression pattern of MAFG-AS1 in the OC tissues and cells. Further mechanistic investigations revealed that MAFG-AS1 upregulated the IGF1 expression pattern through recruitment of NFKB1, whereas MAFG-AS1 upregulated the NFKB1 expression pattern through binding to miR-339-5p. Thus, MAFG-AS1 overexpression accelerated the EMT, invasion, and migration of OC cells, which could be annulled by silencing of IGF1 or NFKB1. Besides, our in vitro findings were successfully recapitulated in the xenograft mice. These results determined that MAFG-AS1 stimulated the OC malignant progression by upregulating the NFKB1-mediated IGF1 via miR-339-5p, thus highlighting a novel potential therapeutic target against OC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Animais , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Subunidade p50 de NF-kappa B , Invasividade Neoplásica/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/genética
12.
Crit Rev Eukaryot Gene Expr ; 31(5): 27-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591387

RESUMO

Gastric cancer is a commonly diagnosed, often fatal malignancy and requires novel anticancer therapies and preventative approaches. This study described the involvement of MAFG-AS1, a lncRNA with important functions in cancer biology, in gastric adenocarcinoma (GA). Thirty-six male and forty-two female GA patients with an average age of 51.9 ± 5.7 years in the range of 35 to 68 years were enrolled. Paired gastric cancer (GC) and non-tumor tissues were collected from each patient. MAFG-AS1 expression was determined. RNA interaction prediction, dual luciferase reporter assay, RT-qPCR assay, Western blot, and CCK-8 assay were conducted. The results indicated that MAFG-AS1 was highly expressed in GA and closely correlated with poor survival. MAFG-AS1 interacted with miR-505, but MAFG-AS1 and miR-505 overexpression showed no significant effects on each other's expression. In addition, MAFG-AS1 increased the expression of PLK1, a miR-505 target. MAFG-AS1 and PLK1 overexpression increased GC cell proliferation rate. MiR-505 overexpression reduced the effects of MAFG-AS1 and PLK1 overexpression on cell proliferation. Therefore, MAFG-AS1 might upregulate PLK1 by sponging miR-505 to promote GA cell proliferation.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Fator de Transcrição MafG/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Transcrição MafG/genética , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Neoplasias Gástricas/genética , Quinase 1 Polo-Like
13.
BMC Cardiovasc Disord ; 21(1): 448, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535081

RESUMO

BACKGROUND: Vascular endothelial cell apoptosis is the leading risk factor of atherosclerosis (AS). The purpose of our study was to use a new generation high-throughput transcription factor (TF) detection method to identify novel key TFs in vascular endothelial cell apoptosis induced by palmitic acid (PA). METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with 0, 300, or 500 µM PA. Candidate TFs in the three groups were identified by differential expression, pathway enrichment, Western Blot (WB), and RT-qPCR analyses. Apoptosis was assessed by fluorescence-activated cell sorting (FACS) using FITC-annexin V and propidium iodide staining. RESULTS: We established a HUVEC apoptosis model to simulate the process of atherosclerosis onset and identified 51 significant TFs. of the 51 TFs, v-maf musculoaponeurotic fibrosarcoma oncogene family protein G (MAFG) and v-maf musculoaponeurotic fibrosarcoma oncogene family protein F (MAFF), were matched to known AS signalling pathways and were validated by WB and RT-qPCR analyses in our study. Overexpression of MAFG or MAFF in HUVECs significantly inhibited PA-induced early apoptosis. CONCLUSIONS: We identified MAFF and MAFG as novel key TFs in vascular endothelial cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Aterosclerose/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fator de Transcrição MafF/metabolismo , Fator de Transcrição MafG/metabolismo , Proteínas Nucleares/metabolismo , Ácido Palmítico/toxicidade , Proteoma , Proteômica , Proteínas Repressoras/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Células Cultivadas , Cromatografia Líquida , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Fator de Transcrição MafF/genética , Fator de Transcrição MafG/genética , Proteínas Nucleares/genética , Mapas de Interação de Proteínas , Proteínas Repressoras/genética , Transdução de Sinais , Espectrometria de Massas em Tandem , Transcrição Gênica
14.
Biochem Biophys Res Commun ; 555: 175-181, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33819748

RESUMO

Microgravity and radiation exposure-induced bone damage is one of the most significant alterations in astronauts after long-term spaceflight. However, the underlying mechanism is still largely unknown. Recent ground-based simulation studies have suggested that this impairment is likely mediated by increased production of reactive oxygen species (ROS) during spaceflight. The small Maf protein MafG is a basic-region leucine zipper-type transcription factor, and it globally contributes to regulation of antioxidant and metabolic networks. Our research investigated the role of MafG in the process of apoptosis induced by simulated microgravity and radiation in MC3T3-E1 cells. We found that simulated microgravity or radiation alone decreased MafG expression and elevated apoptosis in MC3T3-E1 cells, and combined simulated microgravity and radiation treatment aggravated apoptosis. Meanwhile, under normal conditions, increased ROS levels facilitated apoptosis and downregulated the expression of MafG in MC3T3-E1 cells. Overexpression of MafG decreased apoptosis induced by simulated microgravity and radiation. These findings provide new insight into the mechanism of bone damage induced by microgravity and radiation during space flight.


Assuntos
Apoptose/efeitos da radiação , Fator de Transcrição MafG/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos da radiação , Proteínas Repressoras/metabolismo , Apoptose/fisiologia , Linhagem Celular , Regulação para Baixo , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Fator de Transcrição MafG/genética , Osteoblastos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/genética , Simulação de Ausência de Peso , Raios X
15.
FASEB J ; 35(5): e21529, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33813778

RESUMO

To identify hepatitis B virus (HBV)-related lncRNA(s), we previously examined the transcription profiles of the HBV-transgenic cell line HepG2-4D14 and parental HepG2 cells by RNA deep sequencing and identified 38 upregulated long noncoding RNAs (lncRNAs). In the present study, the lncRNA MAFG-AS1 is investigated in detail because its gene is located adjacent to the MAFG gene, which is an important transcription factor involved in cell proliferation. The level of MAFG-AS1 is significantly higher in HCC tissue than in nontumor tissues. TCGA data show that the expression level of MAFG-AS1 is negatively correlated with survival of HCC patients. GEO cohort data show that compared with healthy tissues, the expression level of MAFG-AS1 is significantly higher in HBV-infected liver tissues. Real-time PCR and luciferase reporter assay data show that HBx can enhance the transcription of MAFG-AS1. Gain-of-function and loss-of-function experiments indicate that MAFG-AS1 promotes proliferation, migration, and invasion of HCC cells. Tumor formation assay results demonstrate that knockdown of MAFG-AS1 significantly inhibits cell proliferation in nude mice. Furthermore, MAFG-AS1 enhances the transcription of adjacent MAFG via E2F1. Additionally, MAFG-AS1 interacts with three subunits (MYH9, MYL12B, and MYL6) of nonmuscle myosin IIA (NM IIA). Knockdown of MAFG-AS1 inhibits ATPase activity of MYH9, interaction of NM IIA subunits, and cell cycle progression. Thus, the lncRNA MAFG-AS1 is upregulated by HBV and promotes proliferation and migration of HCC cells. Our findings suggest that MAFG-AS1 is a potential oncogene that may contribute to HBV-related HCC development.


Assuntos
Carcinoma Hepatocelular/patologia , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição MafG/metabolismo , Miosina não Muscular Tipo IIA/química , Proteínas Repressoras/metabolismo , Transativadores/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fator de Transcrição MafG/antagonistas & inibidores , Fator de Transcrição MafG/genética , Miosina não Muscular Tipo IIA/genética , Miosina não Muscular Tipo IIA/metabolismo , Oligonucleotídeos Antissenso/genética , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Transativadores/genética , Proteínas Virais Reguladoras e Acessórias/genética
16.
Sci Bull (Beijing) ; 66(17): 1773-1788, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36654385

RESUMO

Though promoting ferroptosis can reduce cisplatin resistance in tumor cells, ferroptosis and cisplatin resistance in bladder urothelial carcinoma (BUC) following long non-coding RNAs (lncRNAs) is largely unknown. Here, we found the highly expressed lncRNA MAF transcription factor G antisense RNA 1 (MAFG-AS1) in BUC, and its inhibition increased the sensitivity of BUC cells to cisplatin by promoting ferroptosis. Mechanically, binding to iron chaperone poly(rC)-binding protein 2 (PCBP2) facilitated the recruitments of MAFG-AS1 to deubiquitinase ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5), thus stabilizing PCBP2 protein itself. Then PCBP2 was confirmed to interact with ferroportin 1 (FPN1), an iron export protein, leading to inhibition of ferroptosis. Moreover, the expression of MAFG-AS1 was regulated by the transcriptional factor MAFG. Interestingly, MAFG-AS1 stimulated MAFG transcription by recruiting histone acetyltransferase p300 (EP300) to promote the histone 3 at lysine 27 (H3K27ac) at genomic locus of MAFG, forming a MAFG-AS1/MAFG positive feedback loop. In patient samples, higher expression of MAFG-AS1 and MAFG in BUC tissues was significantly correlated with T status and N status, such that MAFG-AS1, MAFG, and the combination of the two were independent prognostic indicators and chemotherapy sensitivity predictive biomarkers for BUC patients. These findings suggest that inhibition of MAFG-AS1 and MAFG can increase the sensitivity of BUC cells to cisplatin through promoting ferroptosis, indicating the novel chemotherapy sensitivity biomarkers and therapeutic target for BUC.


Assuntos
Carcinoma de Células de Transição , Ferroptose , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Retroalimentação , Ferroptose/genética , Fator de Transcrição MafG/genética , Proteínas Repressoras/genética , Proteínas de Ligação a RNA , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
17.
Pathobiology ; 87(6): 345-355, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33238264

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are potential biomarkers that are very important for the development of cancer. Studies show that lncRNAs are significantly correlated with the carcinogenesis and progression of bladder cancer (BLCA). In this research, we aimed at probing into the role of lncRNA MAFG-AS1 in the tumorigenesis of BLCA. METHODS: RT-qPCR was employed to detect MAFG-AS1 expression in BLCA tissues and cells. MAFG-AS1 siRNA and overexpression plasmid were transfected into 5637 and T24 BLCA cell lines to inhibit or upregulate MAFG-AS1 expression, respectively, and then the regulatory functions of MAFG-AS1 on BLCA cell proliferation, migration, and invasion were assessed using cell counting kit-8 (CCK-8) assay, EdU method, and Transwell experiments, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation were conducted to validate the targeting relationships between MAFG-AS1 and miR-143-3p, and miR-143-3p and COX-2. In addition, miR-143-3p was repressed in MAFG-AS1-silenced 5637 and T24 cell lines, and the function of MAFG-AS1/miR-143-3p axis in BLCA cells was further evaluated. The regulatory effects of MAFG-AS1 and miR-143-3p on the expression of COX-2 protein were detected by Western blot. RESULTS: MAFG-AS1 was remarkably upregulated in BLCA patient tissues and cell lines, and its high expression was closely related to histological grade, tumor size, and lymph node metastasis. Silencing of MAFG-AS1 inhibited BLCA cell proliferation, metastasis, and invasion, while overexpression of MAFG-AS1 in BLCA cells had opposite biological effects. MAFG-AS1 was proved to target miR-143-3p to repress its expression. Moreover, it was confirmed that MAFG-AS1 and miR-143-3p could modulate COX-2 expression. CONCLUSION: The MAFG-AS1/miR-143-3p/COX-2 axis contributes to BLCA progression.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Fator de Transcrição MafG/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclo-Oxigenase 2/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/classificação , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Regulação para Cima
18.
Aging (Albany NY) ; 12(20): 20658-20683, 2020 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098638

RESUMO

Hormone receptor-positive breast cancer accounts for around 75% of breast cancers. The estrogen receptor pathway promotes tumor progression and endocrine resistance. Recently, the cross-talk between the ER signaling pathway and cell cycle regulation has been identified. It is necessary to determine the underlying molecular mechanisms involved in the ER signaling pathway and find new target genes for prognosis and drug resistance in ER+ breast cancer. In this study, lncRNA MAFG-AS1 was shown to be up-regulated and associated with poor prognosis in ER+ breast cancer. Functionally, down-regulation of MAFG-AS1 could inhibit cell proliferation and promote apoptosis. In addition, MAFG-AS1 which contained an estrogen-responsive element could promote CDK2 expression by sponging miR-339-5p. Subsequently, MAFG-AS1 and CDK2 were found to be up-regulated in tamoxifen-resistant MCF-7 cells. Cross-talk between the ER signaling pathway and cell cycle conducted by MAFG-AS1 and CDK2 could promote tamoxifen resistance. In conclusion, our study indicated that estrogen-responsive lncRNA MAFG-AS1 up-regulated CDK2 by sponging miR-339-5p, which promoted ER+ breast cancer proliferation. Cross-talk between the ER signaling pathway and cell cycle suggested that lncRNA MAFG-AS1 is a potential biomarker and therapeutic target in ER+ breast cancer. CDK2 inhibitors may be applied to endocrine resistance therapy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinase 2 Dependente de Ciclina/fisiologia , Resistencia a Medicamentos Antineoplásicos , Fator de Transcrição MafG/fisiologia , MicroRNAs/fisiologia , RNA Longo não Codificante , Receptor Cross-Talk , Receptores de Estrogênio/fisiologia , Proteínas Repressoras/fisiologia , Transdução de Sinais , Tamoxifeno/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quinase 2 Dependente de Ciclina/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Fator de Transcrição MafG/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Repressoras/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-32371093

RESUMO

The farnesoid-X-receptor (FXR) is validated target in the cholestatic disorders treatment. Obeticholic acid (OCA), the first in class of FXR agonist approved for clinical use, causes side effects including acute liver decompensation when administered to cirrhotic patients with primary biliary cholangitis at higher than recommended doses. The V-Maf avian-musculoaponeurotic-fibrosarcoma-oncogene-homolog-G (Mafg) and nuclear factor-erythroid-2-related-factor-2 (Nrf2) mediates some of the downstream effects of FXR. In the present study we have investigated the role of FXR/MafG/NRF2 pathway in the development of liver toxicity caused by OCA in rodent models of cholestasis. Cholestasis was induced by bile duct ligation (BDL) or administration of α-naphtyl-isothiocyanate (ANIT) to male Wistar rats and FXR-/- and FXR+/+ mice. Treating BDL and ANIT rats with OCA exacerbated the severity of cholestasis, hepatocytes injury and severely downregulated the expression of basolateral transporters. In mice, genetic ablation FXR or its pharmacological inhibition by 3-(naphthalen-2-yl)-5-(piperidin-4-yl)-1,2,4-oxadiazole rescued from negative regulation of MRP4 and protected against liver injury caused by ANIT. By RNAseq analysis we found that FXR antagonism effectively reversed the transcription of over 2100 genes modulated by OCA/ANIT treatment, including Mafg and Nrf2 and their target genes Cyp7a1, Cyp8b1, Mat1a, Mat2a, Gss. Genetic and pharmacological Mafg inhibition by liver delivery of siRNA antisense or S-adenosylmethionine effectively rescued from damage caused by ANIT/OCA. In contrast, Nrf2 induction by sulforaphane was protective. CONCLUSIONS: Liver injury caused by FXR agonism in cholestasis is FXR-dependent and is reversed by FXR and Mafg antagonism or Nrf2 induction.


Assuntos
Ácido Quenodesoxicólico/análogos & derivados , Colestase/metabolismo , Hepatopatias/metabolismo , Receptores Citoplasmáticos e Nucleares/agonistas , Animais , Ácido Quenodesoxicólico/farmacologia , Colestase/complicações , Colestase/genética , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/genética , Fator de Transcrição MafG/antagonistas & inibidores , Fator de Transcrição MafG/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/genética , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética
20.
Cell Cycle ; 19(5): 601-609, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32079456

RESUMO

MAFG antisense 1 (MAFG-AS1) is recently identified as a novel lncRNA and serves as a tumor promoter in several types of human tumor. However, no prior study has been performed to evaluate the role of MAFG-AS1 in gastric cancer. In our study, we found MAFG-AS1 expression was increased in gastric cancer tissue samples compared with normal gastric mucosa tissue samples, and associated with poor overall survival in gastric cancer patients at The Cancer Genome Atlas database. Furthermore, we confirmed the clinical and prognostic significance of MAFG-AS1 in gastric cancer. We found gastric cancer tissues and cell lines had remarkably increased MAFG-AS1 expression in comparison to normal gastric mucosa tissues and normal human gastric epithelial cell line, and high MAFG-AS1 expression was positively associated with diffuse type, advanced clinical stage, extensive depth of invasion, more lymph node metastasis, and present distant metastasis in gastric cancer patients. Moreover, high MAFG-AS1 expression acted as one of the independent poor prognostic factors for overall survival in gastric cancer patients. The loss-of-function study showed knocking down MAFG-AS1 expression inhibited gastric cancer cell proliferation, migration and invasion in vitro. In conclusion, MAFG-AS1 is probable to be a valuable prognostic biomarker, and a novel potential target for gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição MafG/genética , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia
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