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Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3

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Oncology research 2025年第1期33卷 103-121页

作者： Yan Lu Kang Wang Yuanhong Peng Meng Chen Lin Zhong Luji Huang f U Cheng Xindan Sheng Xin Yang Manzhao Ouyang george A Calin Zhiwei He China-America Cancer Research Institute Guangdong Medical University Dongguan 523808 China. GCP Center Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China. Department of Gastrointestinal Surgery Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China. The Second School of Clinical Medicine Southern Medical University Guangzhou 510080 China. Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA. Department of Oncology Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China.

Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays, which identified the specific action sites of interaction. The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR (qPCR). experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis. Additionally, the regulatory impact of hsa-miR-214-3p on B7H3 was examined. Enzyme-linked immunosorbent assays (ELISA) and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells (PBMCs) on immune cells and associated cytokines.Results:In breast cancer tissues, the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p, as well as with the regulatory effects on breast cancercell behavior. Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3. Importantly, our research identified, for the first time, two binding sites for hsa-miR-214-3p on the 3' UTR of B7H3, both of which exert similar effects independently. Co-culture experime

关键词： B7H3 Breast cancer Hsa-miR-214-3p Immunotherapy

Inference of phylogenetic relationships among key angiosperm lineages using a compatibility method on a molecular data set

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植物分类学报 2008年第2期46卷 130-141页

作者： george f.ESTABROOK Department of Ecology & Evolutionary Biology The University of Michigan Ann Arbor MI 48109-1048 USA

Phylogenetic relationships among the five key angiosperm lineages, Ceratophyllum, Chloranthaceae, eudicots, magnoliids, and monocots, have resisted resolution despite several large-scale analyses sampling taxa and characters extensively and using various analytical methods. Meanwhile, compatibility methods, which were explored together with parsimony and likelihood methods during the early development stage of phylogenetics, have been greatly under-appreciated and not been used to analyze the massive amount of sequence data to recon-struct the basal angiosperm phylogeny. In this study, we used a compatibility method on a data set of eight genes (mitochondrial atp1, matR, and nad5, plastid atpB, matK, rbcL, and rpoC2, and nuclear 18S rDNA) gathered in an earlier study. We selected two sets of characters that are compatible with more of the other characters than a random character would be with at probabilities of pMf the 8 gene pMf other compatible site matrices produced different topologies that were all weakly sup-ported. The topology reconstructed in the parsimony analyses agrees with the one recovered in the previous study using both parsimony and likelihood methods when no character was eliminated. Parts of this topology have also been recovered in several earlier studies. Hence, this topology plausibly reflects the true relationships among the five key angiosperm lineages.

关键词：系统发育被子植物形态特征数据库

fifty years of character compatibility concepts at work

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植物分类学报 2008年第2期46卷 109-129页

作者： george f.ESTABROOK Department of Ecology and Evolutionary Biology The University of Michigan Ann Arbor MI 4809-1048 USA

In the mid 19th century, systematic biologists realized that observable similarities and differences among a group of related species could be the basis for hypotheses about the evolutionary relationships among the species and their ancestors. Such hypotheses can be expressed as characters. A character is comprised of two or more character states of species considered to be similar with respect to a basis for comparison. The states of a character may also be arranged into a character state tree to hypothesize speciation events associated with changes from one character state to another. In the mid 20th century, some systematists realized that sometimes pairs of characters （or character state trees） could be incompatible as hypotheses, i.e., they could not both be true. Through the 1950s, ＇60s and ＇70s, tests for, and ways to resolve, incompatibilities were used to estimate an ancestor rela-tion based on mutually compatible characters. An estimate was often shown as a diagram connecting ancestors to their immediate descendants （not quite correctly） called a phylogenetic tree. More recently, other applications of compatibility concepts have been developed, including： identify characters that appear to be random in the context of their data set; combine estimates of ancestor relations for subsets of taxa in a larger collection into a single estimate （a so-called supertree） for the whole collection; and interpret geographic patterns in an evolutionary context.

关键词： biogeography character compatibility character evaluation convex groups phylogenetic trees,reciprocal illumination speciation supertrees

Did ZIKV evolve to be more dangerous? A new clue towards neurovirulence

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National Science Review 2018年第2期5卷 121-122页

作者： Gary Wong george f.Gao Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Third People's Hospital CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences

Before 2015,Zika virus(ZIKV)was a little-known flavivirus that caused sporadic symptomatic infections in humans(under 20 reported cases,but likely manymore unreported asymptomatic cases)in the decades following its di... 详细信息

关键词： ZIKA virus fLAVIVIRUSES EPIDEMICS

It is not just AIV:from avian to swine-origin influenza virus

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Science China(Life Sciences) 2010年第1期53卷 151-153页

作者： GAO george f CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing Institutes of Life Science Chinese Academy of Sciences

In March and early April 2009,a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States. The virus spreads worldwide by human-to-human transmission.

关键词： gene In It is not just AIV

Stable non-synonymous substitutions on NS gene (NS1 and NS2 proteins) of Qinghai lake H5N1 influenza virus (Clade 2.2) after successive passages in Muscovy ducks

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Science China(Life Sciences) 2009年第9期52卷 847-853页

作者： GAO george f. Key Laboratory of Pathogenic Microbiology and Immunology of CAS (CASPMI) Institute of Microbiology Chinese Academy of Sciences (CAS) China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology Institute of Microbiology Chinese Academy of Sciences Graduate University of Chinese Academy of Sciences Beijing Institutes of Life Science Chinese Academy of Sciences

Although worldwide concern has been raised since the large-scale outbreak of highly pathogenic avian influenza in wild birds at Qinghai Lake,China in 2005,the factors responsible for the ability to kill waterfowl remain unclear. The why and how questions of the H5N1 virus species-jump into its reservoir host need to be answered. In this report we test the pathogenicity and adaptation of Qinghai Lake (Clade 2.2) isolate to Muscovy ducks for further understanding of this virus. The isolate was highly pathogenic in ducks and retained its high pathogenicity even after 20 generations of passage in ducks. During the process of serial passages,only the NS gene developed non-synonymous substitutions,which caused two mutations in NS1 protein (Val23Ala and Leu207Pro) and one in NS2 (Phe55Leu). These mutations persisted immutably through all subsequent passages and the pathogenicity remained high,implying that highly pathogenic H5N1 virus remains stable in aquatic birds through oral transmission. Although the exact functions of these mutations are not known,our results provide an important foundation for further understanding the characteristics of the Qinghai Lake isolates.

关键词： avian influenza virus H5N1 mutation NS1/2 serial passages

CD8:Adhesion Molecule,Co-Receptor and Immuno-Modulator

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Cellular & Molecular Immunology 2004年第2期1卷 81-88页

作者： David K Cole george f Gao Nuffield Department of Clinical Medicine John Radcliffe HospitalUniversity of OxfordHeadington Oxford OX3 9DUUnited Kingdom.

CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes,which are important components in cellular immunity,*** the immune response to cancer and chronic *** are two forms of CD8, either as an αα homodimer or αβ *** acts as an“assistant”or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor(αβTCR)and its ligand peptide major histocompatibility complex(pMHC).CD8 also binds to pMHC but away from the interface of pMHC and TCR contact,thereof no influence on the specificity of this *** the TCR and CD8 bind to the same pMHC at the same time,CD8 is defined as a co-receptor,functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway;if CD8 binds to pMHC independently of the TCR,it is defined as an adhesion *** present,the co-receptor function theory is dominated in the field. Recent study has also shown that murine CD8αα binds to TL antigen,an MHC homologue,therefore acts as an *** this review,we discuss these current understandings of the three aspects of the CD8 functions and their structural *** & Molecular Immunology.2004;1(2):81-88.

关键词： CD8 T cell adhesion co-receptor immuno-modulator

Geneformer:a deep learning model for exploring gene networks

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Science China(Life Sciences) 2023年第12期66卷 2952-2954页

作者： Yuxuan Zheng george f.Gao CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of the Chinese Academy of SciencesBeijing 100049China

Uncovering gene regulatory networks is vital for identifying core regulators,understanding disease progression mechanisms,and identifying potential therapeutic targets,in which large amounts of transcriptome data are ***,most research projects face limitations in obtaining only limited data,constrained by factors such as individual heterogeneity and sequencing technology.

关键词： technology networks identifying

In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009

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Science China(Life Sciences) 2010年第6期53卷 633-642页

作者： Christopher VAVRICKA GAO george f CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences Graduate University of Chinese Academy of Sciences China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology Institute of MicrobiologyChinese Academy of Sciences Beijing Institutes of Life Science Chinese Academy of Sciences

The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health *** order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza *** analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other *** compared their differences and similarities *** on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,*** D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported *** HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion *** 2009 S-OIV HA also has an extra glycosylation site at position *** of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation *** previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were *** results are critical for understanding the pathogenicity of the virus and host immune response against the virus.

关键词： 2009 S-OIV hemagglutinin in silico structural and functional modules