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Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 376-380 doi: 10.1007/s11684-012-0228-0

摘要：

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

关键词： FOXO3a     FOXM1     transcription factor     cancer     drug resistance     tumorigenesis    

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The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 412-425 doi: 10.1007/s11684-018-0650-z

摘要：

Transcription factor networks have evolved in order to control, coordinate, and separate, the functions of distinct network modules spatially and temporally. In this review we focus on the MYC network (also known as the MAX-MLX Network), a highly conserved super-family of related basic-helix-loop-helix-zipper (bHLHZ) proteins that functions to integrate extracellular and intracellular signals and modulate global gene expression. Importantly the MYC network has been shown to be deeply involved in a broad spectrum of human and other animal cancers. Here we summarize molecular and biological properties of the network modules with emphasis on functional interactions among network members. We suggest that these network interactions serve to modulate growth and metabolism at the transcriptional level in order to balance nutrient demand with supply, to maintain growth homeostasis, and to influence cell fate. Moreover, oncogenic activation of MYC and/or loss of a MYC antagonist, results in an imbalance in the activity of the network as a whole, leading to tumor initiation, progression and maintenance.

关键词： network     transcription     cancer     MYC     MAX     MLX    

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RECENT ADVANCES IN THE REGULATION OF CLIMACTERIC FRUIT RIPENING: HORMONE, TRANSCRIPTION FACTOR AND EPIGENETIC

《农业科学与工程前沿（英文）》 2021年 第8卷 第2期

摘要：

Fruit ripening is a complex developmental process made up of genetically programmed physiological and biochemical activities. It culminates in desirable changes in the structural and textural properties and is governed by a complex regulatory network. Much is known about ethylene, one of the most important metabolites promoting the ripening of climacteric fruits. However, the dynamic interplay between phytohormones also plays an important part. Additional regulatory factors such as transcription factors (TFs) and epigenetic modifications also play vital role in the regulation of climacteric fruit ripening. Here, we review and evaluate the complex regulatory network comprising interactions between hormones and the action of TFs and epigenetic modifications during climacteric fruit ripening.

 

关键词： climacteric fruit ripening / phytohormones / TFs / epigenetic modifications    

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RECENT ADVANCES IN THE REGULATION OF CLIMACTERIC FRUIT RIPENING: HORMONE, TRANSCRIPTION FACTOR AND EPIGENETIC

Yinglin JI, Mingyang XU, Aide WANG

《农业科学与工程前沿（英文）》   页码 314-334 doi: 10.15302/J-FASE-2021386

摘要： Fruit ripening is a complex developmental process made up of genetically programmed physiological and biochemical activities. It culminates in desirable changes in the structural and textural properties and is governed by a complex regulatory network. Much is known about ethylene, one of the most important metabolites promoting the ripening of climacteric fruits. However, the dynamic interplay between phytohormones also plays an important part. Additional regulatory factors such as transcription factors (TFs) and epigenetic modifications also play vital role in the regulation of climacteric fruit ripening. Here, we review and evaluate the complex regulatory network comprising interactions between hormones and the action of TFs and epigenetic modifications during climacteric fruit ripening.

关键词： climacteric fruit ripening     phytohormones     TFs     epigenetic modifications    

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Characterization of chromatin accessibility in psoriasis

《医学前沿（英文）》 2022年 第16卷 第3期   页码 483-495 doi: 10.1007/s11684-021-0872-3

摘要： The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.

关键词： psoriasis     ATAC-seq     epigenetics     transcription factor    

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Cloning of human XAF1 gene promoter and assay of its transcription activity in a variety of cell lines

Qiong CHEN, Qing YU, Yuhu SONG, Peiyuan Li, Ying CHANG, Zhijun WANG, Lifeng LIU, Wei WU, Jusheng LIN

《医学前沿（英文）》 2009年 第3卷 第2期   页码 148-152 doi: 10.1007/s11684-009-0032-7

摘要： To investigate the regulation of tumor suppressor XAF1 gene expression in digestive system cancers, we studied XAF1 gene promoter transcription activity and mRNA level in digestive system cancer cell lines (human hepatoma cell line HepG2, human colon cancer cell line LoVo, and human gastric cancer cell line AGS) and nontumor cell lines (human embryonic liver cell line L02 (L02 cells) and human embryonic kidney 293 cells [HEK293 cells]) as controls. 1395-bp-promoter fragment of XAF1 gene was amplified by polymerase chain reaction (PCR) and cloned into pGL3-basic vector and pEGFP-1 vector to assay its promoter transcription activity. The plasmids were transfected into a variety of cell lines by lipofectamine 2000. The promoter transcription activity was determined by dual-luciferase report assay, and enhanced green fluorescent protein (EGFP)-positive cells were detected by fluorescence microscope. The expression of XAF1 mRNA in HEK293 and L02 were significantly higher than that in any of the three digestive system cancer cell lines. The dual-luciferase reporter assay showed that the promoter transcription activity in digestive system tumor cell lines transfected with pGL3-XAF1p promoter was apparently lower than that of both HEK293 and L02 cells. Expression of green fluorescent protein (GFP) under the control of XAF1 promoter in the three digestive system cancer cell lines was lower than that of both HEK293 and L02 cells. The activities of pGL3-XAF1p in the three digestive system cancer cell lines after treatment with heat stress were significantly lower than those in the unstressed cells. The results suggested that remarkably down-regulated XAF1 mRNA expression in digestive system cancer cell lines may be due to loss of transcription activity of XAF1 promoter.

关键词： gene     X-linked inhibitor of apoptosis protein associated factor-1 (XAF1)     promoter     transcription regulation    

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Targeting “undruggable” c-Myc protein by synthetic lethality

Chen Wang, Hui Fang, Jiawei Zhang, Ying Gu

《医学前沿（英文）》 2021年 第15卷 第4期   页码 541-550 doi: 10.1007/s11684-020-0780-y

摘要： Synthetic lethal screening, which exploits the combination of mutations that result in cell death, is a promising method for identifying novel drug targets. This method provides a new avenue for targeting “undruggable” proteins, such as c-Myc. Here, we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network, whose inhibition may cause a catastrophe for tumor cell destiny but not for normal cells. We further discuss strategies to identify these functional nodes in the context of synthetic lethality. We review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently.

关键词： synthetic lethality     undruggable     transcription factor     c-Myc    

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The genetic regulation of skeletal muscle development: insights from chicken studies

Wen LUO, Bahareldin A. ABDALLA, Qinghua NIE, Xiquan ZHANG

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 295-304 doi: 10.15302/J-FASE-2017159

摘要： Skeletal muscle development is a complex multi-process trait regulated by various genetic factors. The chicken embryo is an ideal model system for studying skeletal muscle development. However, only a small proportion of the genetic factors affecting skeletal muscle development have been identified in chicken. The aim of this review is to summarize recent knowledge about the genetic factors involved in the regulation of skeletal muscle development in the chicken, such as gene polymorphisms, epigenetic modification, noncoding RNAs and transcription factors, which can influence skeletal muscle development at the genome, epigenome, transcriptome and proteome levels. Research on the regulation of skeletal muscle development in chicken is not yet comprehensive and most of the candidate genes and single nucleotide polymorphisms related to chicken muscle growth remain to be verified in experimental studies. In addition, the data derived from transcriptome sequencing and genome-wide association studies still require further investigation and analysis and comprehensive studies on the regulation of chicken skeletal muscle development will continue as a major research focus.

关键词： chicken     epigenetic modification     miRNAs     skeletal muscle development     SNP     transcription factor    

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Genetic biosensors for small-molecule products: Design and applications in high-throughput screening

Qingzhuo Wang,Shuang-Yan Tang,Sheng Yang

《化学科学与工程前沿（英文）》 2017年 第11卷 第1期   页码 15-26 doi: 10.1007/s11705-017-1629-z

摘要： Overproduction of small-molecule chemicals using engineered microbial cells has greatly reduced the production cost and promoted environmental protection. Notably, the rapid and sensitive evaluation of the concentrations of the desired products greatly facilitates the optimization process of cell factories. For this purpose, many genetic components have been adapted into biosensors of small molecules, which couple the intracellular concentrations of small molecules to easily detectable readouts such as fluorescence, absorbance, and cell growth. Such biosensors allow a high-throughput screening of the small-molecule products, and can be roughly classified as protein-based and RNA-based biosensors. This review summarizes the recent developments in the design and applications of biosensors for small-molecule products.

关键词： biosensor     small molecule product     transcription factor     riboswitch     high-throughput screening    

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Oocyte-associated transcription factors in reprogramming after somatic cell nuclear transfer: a review

Fengxia YIN,Hui LIU,Shorgan BOU,Guangpeng LI

《农业科学与工程前沿（英文）》 2014年 第1卷 第2期   页码 104-113 doi: 10.15302/J-FASE-2014003

摘要： Oocytes are unique cells with the inherent capability to reprogram nuclei. The reprogramming of the somatic nucleus from its original cellular state to a totipotent state is essential for term development after somatic cell nuclear transfer. The nuclear-associated factors contained within oocytes are critical for normal fertilization by sperm or for somatic cell nuclear reprogramming. The chromatin of somatic nuclei can be reprogrammed by factors in the egg cytoplasm whose natural function is to reprogram sperm chromatin. The oocyte first obtains its reprogramming capability in the early fetal follicle, and then its capacity is enriched in the late growth phase and reaches its highest capability for reprogramming as fully-grown germinal vesicle oocytes. The cytoplasmic milieu most likely contains all of the specific transcription and/or reprogramming factors necessary for cellular reprogramming. Certain transcription factors in the cytoplast may be critical as has been demonstrated for induced pluripotent stem cells. The maternal pronucleus exerts a predominant, transcription-dependent effect on embryo cytofragmentation, with a lesser effect imposed by the ooplasm and the paternal pronucleus. With deep analysis of transcriptomics in oocytes and early developmental stage embryos more maternal transcription factors inducing cellular reprogramming will be identified.

关键词： nuclear reprogramming     somatic cell     transcription factors     transcriptomics    

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Expression of STAT6 and NF-κB p65 in the colon mucosa of patients with ulcerative colitis

Rui ZHU MD, Heng FAN MD, Lin SHEN MD, Jianguo LIU BD, Jia ZHAO MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 475-479 doi: 10.1007/s11684-009-0086-6

摘要： The expression of signal transducer and activator of transcription 6 (STAT6) and nuclear factor-κB (NF-κB) in the colonic mucosa of patients with ulcerative colitis (UC) was examined. Real-time polymerase chain reaction and immunohistochemistry were used to detect the expression of STAT6 and NF-κB p65 at both mRNA and protein levels in the colonic mucosa of patients with UC and healthy volunteers. The results showed that the expression levels of STAT6 and NFκB p65 in the colonic mucosa of patients with UC were significantly higher than in normal controls at both mRNA and protein levels. These data suggest that STAT6 and NFκB p65 perhaps play an important role in the pathogenesis of UC and underscore the potential value of anti-UC strategies in the clinical management of this disease.

关键词： ulcerative colitis     signal transducer and activator of transcription 6 (STAT6)     nuclear factor-κ     B p65 (NF-κ     B p65)    

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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

《工程（英文）》 2024年 第32卷 第1期   页码 58-69 doi: 10.1016/j.eng.2023.09.019

摘要：

Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9)     Epigenetics     Hepatocyte nuclear factor 1 alpha (HNF1A)     Hepatocyte nuclear factor 4 alpha (HNF4A)     Forkhead box protein A2 (FOXA2)     N-glycosylation     HepG2 cells    

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LSSVM-based approach for refining soil failure criteria and calculating safety factor of slopes

Shiguo XIAO; Shaohong LI

《结构与土木工程前沿（英文）》 2022年 第16卷 第7期   页码 871-881 doi: 10.1007/s11709-022-0863-8

摘要： The failure criteria of practical soil mass are very complex, and have significant influence on the safety factor of slope stability. The Coulomb strength criterion and the power-law failure criterion are classically simplified. Each one has limited applicability owing to the noticeable difference between calculated predictions and actual results in some cases. In the work reported here, an analysis method based on the least square support vector machine (LSSVM), a machine learning model, is purposefully provided to establish a complex nonlinear failure criterion via iteration computation based on strength test data of the soil, which is of more extensive applicability to many problems of slope stability. In particular, three evaluation indexes including coefficient of determination, mean absolute percentage error, and mean square error indicate that fitting precision of the machine learning-based failure criterion is better than those of the linear Coulomb criterion and nonlinear power-law criterion. Based on the proposed LSSVM approach to determine the failure criterion, the limit equilibrium method can be used to calculate the safety factor of three-dimensional slope stability. Analysis of results of the safety factor of two three-dimensional homogeneous slopes shows that the maximum relative errors between the proposed approach and the linear failure criterion-based method and the power-law failure criterion-based method are about 12% and 7%, respectively.

关键词： slope stability     safety factor     failure criterion     least square support vector machine    

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lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

《医学前沿（英文）》 2023年 第17卷 第2期   页码 317-329 doi: 10.1007/s11684-022-0931-4

摘要： Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.

关键词： lncR-GAS5     miR-193-5p     splicing factor SRSF10     autophagy     atherogenesis    

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The calculation of equivalence factor for ecological footprints in China: a methodological note

Moucheng LIU,Wenhua LI,Dan ZAHNG,Ning SU

《环境科学与工程前沿（英文）》 2015年 第9卷 第6期   页码 1015-1024 doi: 10.1007/s11783-014-0670-0

摘要： The Ecological Footprint (EF), a physical indicator to measure the extent of humanity’s use of natural resources, has gained much attention since it was first used by Wackernagel and Rees in 1996. In order to appraise land area types with different levels of productivity, they introduced the concept of an equivalence factor. This relates to the average primary biomass productivities of different types of land (i.e. arable land, pasture, forest, water/fishery, built-up land and fossil energy land) to the regional average primary biomass productivity of all land types in a given year. Hence, the equivalence factor is an important parameter in the EF model and it directly affects the reliability of all results. Thus, this article calculates equivalence factors on the national and provincial levels in China based on Net Primary Production (NPP) from MODIS 1 km data in 2008. Firstly, based on the Light Utility Efficiency and CASA model, the NPP of different biologically productive lands of China and of different provinces was calculated. Secondly, China’s equivalence factor for 6 land area types was calculated based on NPP: arable land and built-up land has an equivalence factor of 1.71, forest and fossil energy land has a factor of 1.41, pasture has a factor of 0.44 and water/fishery 0.35; Finally, the equivalence factor of 6 land area types in different provinces was also calculated. The NPP of each ecosystem type varies along with the equivalence factor in different provinces. However, the ranking of the equivalence factors in different provinces remain the same, with that of arable land being the largest, and the water/fishery being the smallest.

关键词： ecological footprint     equivalence factor     net primary production     biological capacity     land types    

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标题 作者 时间 类型 操作

Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

期刊论文

The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

null

期刊论文

RECENT ADVANCES IN THE REGULATION OF CLIMACTERIC FRUIT RIPENING: HORMONE, TRANSCRIPTION FACTOR AND EPIGENETIC

期刊论文

RECENT ADVANCES IN THE REGULATION OF CLIMACTERIC FRUIT RIPENING: HORMONE, TRANSCRIPTION FACTOR AND EPIGENETIC

Yinglin JI, Mingyang XU, Aide WANG

期刊论文

Characterization of chromatin accessibility in psoriasis

期刊论文

Cloning of human XAF1 gene promoter and assay of its transcription activity in a variety of cell lines

Qiong CHEN, Qing YU, Yuhu SONG, Peiyuan Li, Ying CHANG, Zhijun WANG, Lifeng LIU, Wei WU, Jusheng LIN

期刊论文

Targeting “undruggable” c-Myc protein by synthetic lethality

Chen Wang, Hui Fang, Jiawei Zhang, Ying Gu

期刊论文

The genetic regulation of skeletal muscle development: insights from chicken studies

Wen LUO, Bahareldin A. ABDALLA, Qinghua NIE, Xiquan ZHANG

期刊论文

Genetic biosensors for small-molecule products: Design and applications in high-throughput screening

Qingzhuo Wang,Shuang-Yan Tang,Sheng Yang

期刊论文

Oocyte-associated transcription factors in reprogramming after somatic cell nuclear transfer: a review

Fengxia YIN,Hui LIU,Shorgan BOU,Guangpeng LI

期刊论文

Expression of STAT6 and NF-κB p65 in the colon mucosa of patients with ulcerative colitis

Rui ZHU MD, Heng FAN MD, Lin SHEN MD, Jianguo LIU BD, Jia ZHAO MM,

期刊论文

转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

期刊论文

LSSVM-based approach for refining soil failure criteria and calculating safety factor of slopes

Shiguo XIAO; Shaohong LI

期刊论文

lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

期刊论文

The calculation of equivalence factor for ecological footprints in China: a methodological note

Moucheng LIU,Wenhua LI,Dan ZAHNG,Ning SU

期刊论文