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Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences/State Key laboratory of Genetic Engineering/Cancer Institutes/Department of Oncology/Key laboratory of Breast Cancer in Shanghai/Shanghai Key laboratory of Medical epigenetics/Shanghai Key laboratory of Radiation Oncology/International Co-laboratory of Medical epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and *** cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and *** have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast *** tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ***,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer *** this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory ***,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during ***,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model

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

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Engineering 2024年第1期 57-68页

作者： Vedrana Vi?i? Bo?kor Nika Foglar Goran Josipovi? Marija Klasi? Ana Vuji? Branimir Plav?a Toma Keser Samira Smajlovi? Aleksandar Vojta Vlatka Zoldo? laboratory for epigenetics Department of Biology Faculty of Science University of Zagreb Genos Glycoscience Research laboratory Faculty of Pharmacy and Biochemistry University of Zagreb

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 *** Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase *** in silico analysis of HNF1A,HNF4A,and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the *** previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma ***,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan *** 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 *** results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many gly co-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan *** effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantenna ry *** 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 *** 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.

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Dip2a regulates stress susceptibility in the basolateral amygdala

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Neural Regeneration Research 2025年第6期20卷 1735-1748页

作者： Jing Li Zixuan He Weitai Chai Meng Tian Huali Yu Xiaoxiao He Xiaojuan Zhu Key laboratory of Molecular epigenetics Ministry of Education Institute of Genetics and CytologyNortheast Normal UniversityChangchunJilin ProvinceChina

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

关键词： 5-hydroxytryptamine acute restraint stress basolateral amygdala CaMKII neurons DIP2A metabolomics neurotransmitters principal component analysis stress susceptibility tryptophan

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Naringin ameliorates H_(2)O_(2)-induced oxidative damage in cells and prolongs the lifespan of female Drosophila melanogaster via the insulin signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1231-1245页

作者： Xiaomei Du Kexin Wang Xiaoyan Sang Xiangxing Meng Jiao Xie Tianxin Wang Xiaozhi Liu Qun Huang Nan Zhang Hao Wang State Key laboratory of Food Nutrition and Safety Tianjin University of Science and TechnologyTianjin 300457China The key laboratory of Environmental Pollution Monitoring and Disease Control Ministry of EducationGuizhou Medical UniversityGuizhou 550025China Department of neurosurgery the Fifth Central Hospital of TianjinTianjin 300450China Tianjin Key laboratory of epigenetics for Organ Department in Preterm Infants the Fifth Central Hospital of TianjinTianjin 300450China

Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological *** this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying *** results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in ***,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde *** also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem ***,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of ***,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.

关键词： Drosophila melanogaster Insulin signaling(IIS)pathway Naringin PC12 cell HepG2 cell

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Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key laboratory of Malignant Tumor epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai Translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment *** to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and *** major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,*** studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell *** ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor ***,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback ***,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor *** also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

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PRC2 primes bivalent genes for transcription induction independent of histone methyltransferase activity

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Science China Life Sciences 2024年第9期67卷 2033-2035页

作者： Meihan Gong Ye Yuan Zhongye Dai Xuejiao Lv Jiacheng Su Dawei Huo Lin Niu Xu Chen Xudong Wu State Key laboratory of Experimental Hematology The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Department of Cell Biology School of Basic Medical Sciences Tianjin Medical University Bone Marrow Transplantation Center the First Affiliated Hospital Zhejiang University School of Medicine Liangzhu Laboratory Institute of Hematology Zhejiang University

Dear Editor,Polycomb group proteins, conserved epigenetic transcriptional repressors, are crucial for orchestrating diverse developmental gene expression programs(Schuettengruber et al., 2017). The polycomb repressive complex 2(PRC2) catalyzes H3 lysine-27 trimethylation(H3K27me3) to establish a delicate balance with H3K4me3, forming a bivalent chromatin state at target gene promoters and thereby poising them for subsequent transcription activation(Bernstein et al.,2006).

关键词： REPRESSIVE COMPLEX 2 POLYCOMB PROMOTERS

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Unraveling the regulatory network of flower coloration in soybean:Insights into roles of GmMYBA3 and GmMYBR1

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The Crop Journal 2024年第2期12卷 443-455页

作者： Ruifang Gao Yueqing Li Yanan Wang Xiaotong Shan Siqi Yang Ye Zhang Saiyu Ma Chunbao Zhang Jianchun Qin Li Wang Xiang Gao College of Plant Science Jilin UniversityChangchun 130062JilinChina Key laboratory of Molecular epigenetics of MOE and Institute of Genetics&Cytology Northeast Normal UniversityChangchun 130024JilinChina Soybean Research Institute National Engineering Research Center for SoybeanJilin Academy of Agricultural SciencesChangchun 130033JilinChina

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering ***,the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans(Glycine max).In this study,we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean *** and genetic studies have characterized two antagonistic regulators,the positive activator GmMYBA3 and the negative repressor GmMYBR1,that modulate the gene expression of anthocyanin biosynthesis in soybean *** findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a,highlighting the complexity of anthocyanin regulation in different soybean *** of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis-related genes,with GmF3’5’H identified as a crucial determinant of white flower *** study provides a molecular mechanism underlying soybean flower color determination,paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.

关键词： Anthocyanin Flower color determination MBW complex MYB repressor Pleiotropic regulator

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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化

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Engineering 2024年第1期32卷 57-68页

作者： Vedrana Vicic Bockor Nika Foglar Goran Josipovic Marija Klasic Ana Vujic Branimir Plavsa Toma Keser Samira Smajlovic Aleksandar Vojta Vlatka Zoldos laboratory for epigenetics Department of BiologyFaculty of ScienceUniversity of ZagrebZagreb 10000Croatia Genos Glycoscience Research laboratory Zagreb 10000Croatia Faculty of Pharmacy and Biochemistry University of ZagrebZagreb 10000Croatia

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,cre-ating a regulatory transcriptional *** Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase *** in silico analysis of HNF1A,*** FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the *** previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma ***,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan *** used the state-of-the-art clus-tered 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 *** results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan *** effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary *** 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 *** 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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Long COVID:From olfactory dysfunctions to viral Parkinsonism

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 137-147页

作者： Sanyukta Pandey Vibha Bapat Jancy Nixon Abraham Nixon M.Abraham Department of Biology Laboratory of Neural Circuits and Behaviour(LNCB)Indian Institute of Science Education and Research(IISER)PuneMaharashtraIndia Department of Life Sciences Centre of Excellence in EpigeneticsShiv Nadar Institution of EminenceGautam Buddha NagarUttar PradeshIndia

Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional ***,the surge of neurological disorders followed the viral pandemics,for example,the emergence of Encephalitis Lethargica after the outbreak of Spanish *** and after COVID-19 infection,the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's *** reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these *** this manuscript,we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical ***,we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.

关键词： long COVID neurodegeneration neurotropism olfactory dysfunctions viral parkinsonism

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Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key laboratory of Medical epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer *** pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal *** targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical ***,to date,the clinical success of drugs targeting the innate immune pathway remains ***,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor *** uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate *** this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell *** propose that within the TME,the innate immune pathway exhibits multidimensional *** diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling *** pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative *** our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

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