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Long noncoding rna LRG modulates Drosophila locomotion by sequestering Synaptotagmin 1 protein

Insect Science 2024年第6期31卷 1756-1769页

作者： Ming-Yang Cui Meng-Bo Xu Ying-Xuan Wang Bao-Yan Bai Run-Sheng Chen Li Liu Mei-Xia Li State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijingChina College of Life Sciences University of Chinese Academy of SciencesBeijingChina Key Laboratory of Noncoding RNA Institute of BiophysicsChinese Academy of SciencesBeijingChina

Apparently,the genomes of many organisms are pervasively transcribed,and long noncoding rnas(lncrnas)make up the majority of cellular *** have been reported to play important roles in many biological processes;however,their effects on locomotion are poorly ***,we presented a novel lncrna,Locomotion Regulatory Gene(LRG),which participates in locomotion by sequestering Synaptotagmin 1(SYT1).LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body,motoneuron or muscle-expression of *** the molecular level,the synaptic vesicles(SVs)release and movement-related SYT1 protein was recognized as LRG-interacting protein ***,LRG had no effects on SYT1 ***,the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of *** together,all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its *** work displays a new function of lncrna and provides insights for revealing the pathogenesis of neurological diseases with motor disorders.

关键词： expression thereby release

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Genomic characterization of peritoneal lavage cytology-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 66-77页

作者： Zhouqiao Wu Tingfei Gu Changxian Xiong Jinyao Shi Jingpu Wang Ting Guo Xiaofang Xing Fei Pang Ning He Rulin Miao Fei Shan Yuan Zhou Ziyu Li Jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Biomedical Informatics Department of Physiology and PathophysiologyCenter for Noncoding RNA MedicineMOE Key Lab of Cardiovascular SciencesSchool of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric ***: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric ***: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

关键词： Cytology gastric carcinoma peritoneal metastasis whole exome sequencing

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Microrna–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 1030-1042页

作者： Yicong Shen Yuanxu Gao Jiangcheng Shi Zhou Huang Rongbo Dai Yi Fu Yuan Zhou Wei Kong Qinghua Cui Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao Special Administrative Region 999078China Department of Biomedical Informatics Center for Noncoding RNA MedicineSchool of Basic Medical SciencesPeking UniversityBeijing 100191China

Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly *** main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug *** medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be ***,we proposed a novel algorithm to quantify disease relations based on a large accumulated microrna–disease association dataset and then built a disease network covering 15 disease classes and 304 *** revealed some patterns for these *** instance,diseases tended to be clustered and coherent in the ***,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in *** on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of ***,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.

关键词： Abdominal aortic aneurysm Network medicine Microrna-derived disease network Autoimmune disease Methotrexate

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Identiffcation and Analysis of Sex-Biased Copy Number Alterations

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Health Data Science 2024年第1期4卷 355-363页

作者： Chenhao Zhang Yang Yang Qinghua Cui Dongyu Zhao Chunmei Cui Department of Biomedical Informatics Center for Noncoding RNA MedicineState Key Laboratory of Vascular Homeostasis and RemodelingSchool of Basic Medical SciencesPeking University38 Xueyuan RdBeijing 100191China Department of Biochemistry and Biophysics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China School of Sports Medicine Wuhan Institute of Physical EducationNo.461 Luoyu Rd.Wuchang DistrictWuhan 430079Hubei ProvinceChina

Background:Sex difference has long been recognized at cancer incidence,outcomes,and responses to *** the somatic mutation proffles of large-scale cancer samples between the sexes have revealed several potential drivers of cancer with sex ***,it is still a demand for indepth scrutinizing the sex-biased characteristics of genome instability to link the clinical differences for individual cancer ***:Here,we utilized a published framework devised to speciffcally compare the copy number proffles between 2 groups to identify the sex-biased copy number alterations(CNAs)across 16 cancer types from the The Cancer Genome Atlas Program database,and dissected the impact of those ***:Totally,81 male-biased CNA regions and 23 female-biased CNA regions in 16 cancer types were *** annotation analysis showed that several critical biological functions associated with sex-biased CNAs are shared in multiple cancer types,including immune-related pathways and regulation of cellular *** sex-biased CNAs have a substantial effect on transcriptional consequence,where the average of over 68%of genes have a linear relationship with CNAs across cancer types,and 14%of those genes are affected by the combination of the sex and copy ***,29 sex-biased CNA regions show latent capacity to be sex-speciffc prognostic biomarker such as CNA on 11q13.4 for head and neck cancer and lung ***:This analysis offers new insights into the role of sex in cancer etiology and prognosis through a detailed characterization of sex differences in genome instability of diverse cancers.

关键词： alterations utilized latent

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Genome-wide long non-coding rna association study on Han Chinese women identifies lncHSAT164 as a novel susceptibility gene for breast cancer

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Chinese Medical Journal 2021年第10期134卷 1138-1145页

作者： Jing-Kai Xu Guo-Zheng Li Zhi Li Wen-Jing Li Run-Sheng Chen Bo Zhang Xue-Jun Zhang Department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityKey Laboratory of DermatologyAnhui Medical UniversityMinistry of EducationHefeiAnhui 230032China Department of Genetics School of Life SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Oncology No.2 HospitalAnhui Medical UniversityHefeiAnhui 230032China Laboratory of Bioinformatics and Noncoding RNA Key Laboratory of RNA BiologyInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

Background:Single-nucleotide polymorphisms(SNPs)-associated genes and long non-coding rnas(lncrnas)can contribute to human *** comprehensively investigate the contribution of lncrnas to breast cancer,we performed the first genome-wide lncrna association study on Han Chinese ***:We designed an lncrna array containing>800,000 SNPs,which was incorporated into a 96-array plate by Affymetrix(CapitalBio Technology,China).Subsequently,we performed a two-stage genome-wide lncrna association study on Han Chinese women covering 11,942 individuals(5634 breast cancer patients and 6308 healthy controls).Additionally,in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated ***:We identified a novel breast cancer-associated susceptibility SNP,rs11066150(P_(meta)=2.34×10^(-8)),and a previously reported SNP,rs9397435(P_(meta)=4.32×10^(-38)),in Han Chinese ***11066150 is located in NONHSAT164009.1(lncHSAT164),which is highly expressed in breast cancer tissues and cell ***164 overexpression promoted colony formation,whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell ***:Based on our lncrna array,we identified a novel breast cancer-associated lncrna and found that lncHSAT164 may contribute to breast cancer by regulating the cell *** findings suggest a potential therapeutic target in breast cancer.

关键词： Breast cancer lncHSAT164 Single-nucleotide polymorphisms

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The novel cereblon modulator CC-885 inhibits mitophagy via selective degradation of BNIP3L

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中国药理学报（英文版） 2020年第9期41卷 1246-1254页

作者： Bing-bing Hao Xiao-jing Li Xing-long Jia Yu-xing Wang Lin-hui Zhai Duan-zhuo Li Jie Liu Die Zhang Yu-lu Chen Yong-hu Xu Sang-kyu Lee Guo-feng Xu Xiao-hua Chen Yong-jun Dang Bin Liu Min-jia Tan The Chemical Proteomics Center and State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China University of Chinese Academy of Sciences Beijing 100049 China Key Laboratory of Metabolism and Molecular Medicine The Ministry of Education Department of Biochemistry and Molecular Biology Shanghai Medical College Fudan University Shanghai 200030 China Lab for Noncoding RNA and Cancer School of Life Science Shanghai University Shanghai 200444 China Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention Hubei Polytechnic University School of Medicine Huangshi 435003 China Department of Pediatric Urology Xinhua Hospital Shanghai Jiao Tong University School of Medicine 1665 Kongjiang St. Shanghai 200092 China BK21 Plus KNU Multi-Omics based Creative Drug Research Team College of Pharmacy and Research Institute of Pharmaceutical Sciences Kyungpook National University Daegu 41566 Republic of Korea Chinese Academy of Sciences Key Laboratory of Receptor Research Synthetic Organic & Medicinal Chemistry Laboratory Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

Mitophagy is a degradative pathway that mediates the degradation of the entire mitochondria,and defects in this process are implicated in many diseases including *** mammals,mitophagy is mediated by BNIP3L (also known as NIX) that is a dual regulator of mitochondrial turnover and programmed cell death *** myeloid leukemia (AML) cells with deficiency of BNIP3L are more sensitive to mitochondria-targeting *** small molecular inhibitors for BNIP3L are currently not *** immunomodulatory drugs (IMiDs) have been proved by FDA for hematologic malignancies,however,the underlining molecular mechanisms are still elusive,which hindered the applications of BNIP3L inhibition for AML *** this study we carried out MS-based quantitative proteomics analysis to identify the potential neosubstrates of a novel thalidomide derivative CC-885 in A549 *** total,we quantified 5029 proteins with 36 downregulated in CRBN+/+ cell after CC-885 *** analysis showed that macromitophagy pathway was enriched in the negative pathway after CC-885 *** further found that CC-885 caused both dose-and time-dependent degradation of BNIP3L in CRBN+/+,but not CRBN-/-***,our data uncover a novel role of CC-885 in the regulation of mitophagy by targeting BNIP3L for CRL4CRBN E3 ligase-dependent ubiquitination and degradation,suggesting that CC-885 could be used as a selective BNIP3L degradator for the further ***,we demonstrated that CC-885 could enhance AML cell sensitivity to the mitochondria-targeting drug rotenone,suggesting that combining CC-885 and mitochondria-targeting drugs may be a therapeutic strategy for AML patients.

关键词： immunomodulatory drugs (IMiDs) CC-885 BNIP3L mitophagy CRBN acute myeloid leukemia mitochondria-targeting drugs

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Identification and Analysis of Human Sex-biased Micrornas

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Genomics, Proteomics & Bioinformatics 2018年第3期16卷 200-211页

作者： Chunmei Cui Weili Yang Jiangcheng Shi Yong Zhou Jichun Yang Qinghua Cui Yuan Zhou Department of Biomedical Informatics Department of Physiology and Pathophysiology Center for Noncoding RNA Medicine MOE Key Laboratory of Cardiovascular Sciences School of Basic Medical Sciences Peking University Department of Physiology and Pathophysiology Center for Noncoding RNA Medicine School of Basic Medical SciencesPeking University Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen Hospital Capital Medical University

Sex differences are widely observed under various circumstances ranging from physiolog- ical processes to therapeutic responses, and a myriad of sex-biased genes have been identified. In recent years, transcriptomic datasets of micrornas （mirnas）, an important class of non-coding rnas, become increasingly accessible. However, comprehensive analysis of sex difference in mirna expression has not been performed. Here, we identified the differentially-expressed miR- NAs between males and females by examining the transcriptomic datasets available in public data- bases and conducted a systemic analysis of their biological characteristics. Consequently, we identified 73 female-biased mirnas （FmiRs） and 163 male-biased mirnas （MmiRs） across four tissues including brain, colorectal mucosa, peripheral blood, and cord blood. Our results suggest that compared to FmiRs, MmiRs tend to be clustered in the human genome and exhibit higher evolutionary rate, higher expression tissue specificity, and lower disease spectrum width. In *** enrichment analysis of mirnas show that FmiR genes are significantly associated with metabolism process and cell cycle process, whereas MmiR genes tend to be enriched for functions like histone modification and circadian rhythm. In all, the identification and analysis of sex-biased mirnas together could provide new insights into the biological differences between females and males and facilitate the exploration of sex-biased disease susceptibility and therapy.

关键词： Sex bias Micrornas Conservation Disease association Personalized medicine

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Muscle-specific histone H3K36 dimethyltransferase SET-18 shortens lifespan of Caenorhabditis elegans by repressing daf-16a expression

Muscle-specific histone H3K36 dimethyltransferase SET-18 sho...

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第五届中国秀丽线虫大会

作者： Liangping Su Hongyuan Li Cheng Huang Tingting Zhao Yongjun Zhang Xueqing Ba Zhongwei Li Yu Zhang Baiqu Huang Jun Lu Yanmei Zhao Xiaoxue Li The Key Laboratory of Molecular Epigenetics of the Ministry of Education Northeast Normal University The Institute of Genetics and Cytology Northeast Normal University Key Laboratory of RNA Biology Beijing Key Laboratory of Noncoding RNAInstitute of BiophysicsCAS Center for Excellence in BiomacromoleculesChinese Academy of Sciences

Mounting evidence shows that histone methylation,a typical epigenetic mark,is crucial for gene expression regulation during *** trimethylation of Lys 36 on histone H3(H3K36me3) in worms and yeast is reported to shorten *** multicellular eukaryotes,H3K36me3 modification is responsible for gene activation,whereas H3K36me2 has a reverse *** function of H3K36me2 in aging remains *** this study,we identified Caenorhabditis elegans SET-18 as a histone H3 K36 ***-18 deletion extended lifespan and increased oxidative stress resistance,dependent on daf-16 activity in the insulin/IGF-1-like *** set-18 mutants,transcription of daf-16 isoform a(daf-16 a) was specifically ***,a decrease in H3K36me2 on daf-16 a promoter was ***-specific expression of SET-18 increased in aged worms(day 7 and day 11),attributable to elevation of global H3K36me2 and inhibition of daf-16 a ***,longevity was *** findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

关键词： SET-18 H3K36me2 modification lifespan daf-16a insulin/IGF-1-like pathway

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Live cell single molecule-guided Bayesian localization super resolution microscopy

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细胞研究（英文版） 2017年第5期27卷 713-716页

作者： Mingshu Zhang Wenting He Zhiyong Liu Fa Zhang Jennifer Lippincott-Schwartz Key Laboratory of RNA Biology Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Beijing Key Laboratory of Noncoding RNA Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Key Lab of Intelligent Information Processing Institute of Computing Technology Chinese Academy of Sciences Beijing 100190 China Janelia Research Campus Howard Hughes Medical Institute Ashburn Virginia 20147 USA

Dear Editor,Many current super resolution (SR) microscopic techniques [1-6] have been successfully applied to image cellular dynamics in living cells,but their applications have remained technically *** cell stimulated emission depletion (STED)/reversible saturable optical linear fluorescence transitions (RESOLFT) microscopy and structured illumination microscopy (SIM)/nonlinear SIM require sophisticated expensive optical setups and specialized expertise for accurate optical *** cell photo-activated localization microscopy (PALM)/stochastic optical reconstruction microscopy (STORM)use less complicated setup;however,a scientific complementary metal-oxide-semiconductor (sCMOS) camera,whose pixel-dependent noise must be characterized and calibrated before use [7],is required for extremely high acquisition speed over tens of thousands of ***,wide field-based SR microscopies have been developed to improve temporal resolution using much fewer time-lapse images (hundreds to thousands) than PALM/STORM [8,9].One of them,Bayesian analysis of the blinking and bleaching (3B) [8],offers enormous potential to resolve ultrastructure and fast cellular dynamics in living cells beyond the diffraction *** its potential,3B analysis is impractical when imaging the nanoscale dynamics in large fields of view over long time periods,as the calculation is extremely time-consuming [8] and/or the analysis consumes large amounts of web resources [10].Another major problem of 3B imaging is the artificial thinning and thickening of structures both in simulated image data and in experimental data [8,10].

关键词： @@

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Extending the spatiotemporal resolution of super-resolution microscopies using photomodulatable °uorescent proteins

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Journal of Innovative Optical Health Sciences 2016年第3期9卷 52-62页

作者： Mingshu Zhang Zhifei Fu Pingyong Xu Key Laboratory of RNA Biology Institute of Biophysics Chinese Academy of Sciences Beijing100101P.R.China Beijing Key Laboratory of Noncoding RNA Institute of Biophysics Chinese Academy of Sciences Beijing100101P.R.China Graduate School of the Chinese Academy of Sciences Beijing P.R.China

In the past two decades,various super-resolution(SR)microscopy techniques have been developed to break the di®raction limit using subdi®raction excitation to spatially modulate the°uorescence ***°uorescent proteins(FPs)can be activated by light of speci¯c wavelengths to produce either stochastic or patterned subdi®raction excitation,resulting in improved optical *** this review,we focus on the recently developed photomodulatable FPs or commonly used SR microscopies and discuss the concepts and strategies for optimizing and selecting the biochemical and photophysical properties of PMFPs to improve the spatiotemporal resolution of SR techniques,especially time-lapse live-cell SR techniques.

关键词： Super-resolution PMFP mGeos mEos3 Skylan-S Skylan-NS

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