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dbDEMC 3.0:Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

Genomics, Proteomics & bioinformatics 2022年第3期20卷 446-454页

作者： Feng Xu Yifan Wang Yunchao Ling Chenfen Zhou Haizhou Wang Andrew E.Teschendorff Yi Zhao Haitao Zhao Yungang He Guoqing Zhang Zhen Yang center for Medical Research and Innovation of Pudong Hospital Fudan University Pudong Medical CenterShanghai 201399China Institutes of Biomedical Science Shanghai Key Laboratory of Medical EpigeneticsInternational Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)Fudan UniversityShanghai 200032China Bio-Med Big Data center CAS Key Laboratory of Computational BiologyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Institute of Computing Technology Chinese Academy of SciencesBeijing 100190China Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China shanghai Fifth People’s Hospital Fudan UniversityShanghai 200240China

MicroRNAs(miRNAs)are important regulators in gene *** dysregulation of miRNA expression is widely reported in the transformation from physiological to pathological states of cells.A large number of differentially expressed miRNAs(DEMs)have been identified in various human cancers by using high-throughput technologies,such as microarray and *** mining of published studies with high-throughput experiment information,the database of DEMs in human cancers(dbDEMC)was constructed with the aim of providing a systematic resource for the storage and query of the *** we report an update of the dbDEMC to version 3.0,which contains two-fold more data entries than the second version and now includes also data from mice and *** dbDEMC 3.0 contains 3268 unique DEMs in 40 different cancer *** current datasets for differential expression analysis have expanded to 9 generalized ***,the current release integrates functional annotations of DEMs obtained by using experimentally validated *** annotations can be of great benefit to the intensive analysis of the roles of DEMs in *** summary,dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human *** dbDEMC 3.0 is freely accessible at https://***/dbDEMC.

关键词： MicroRNA Cancer Differential expression Model organism Database

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Expanding the Coverage of Metabolic Landscape in Cultivated Rice with Integrated Computational Approaches

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Genomics, Proteomics & bioinformatics 2022年第4期20卷 702-714页

作者： Xuetong Li Hongxia Zhou Ning Xiao Xueting Wu Yuanhong Shan Longxian Chen Cuiting Wang Zixuan Wang Jirong Huang Aihong Li Xuan Li CAS Key Laboratory of Synthetic Biology/National center for Gene Research CAS Center for Excellence in Molecular Plant Sciences/Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China Lixiahe Agricultural Research Institute of Jiangsu Province Yangzhou 225007China shanghai Key Laboratory of Plant Molecular Sciences College of Life SciencesShanghai Normal UniversityShanghai 200234China University of Chinese Academy of Sciences Beijing 100049China

Genome-scale metabolomics analysis is increasingly used for pathway and function discovery in the post-genomics *** great potential offered by developed mass spectrometry(MS)-based technologies has been hindered,since only a small portion of detected metabolites were identifiable so *** address the critical issue of low identification coverage in metabolomics,we adopted a deep metabolomics analysis strategy by integrating advanced algorithms and expanded reference *** experimental reference spectra and in silico reference spectra were adopted to facilitate the structural *** further characterize the structure of metabolites,two approaches were incorporated into our strategy,i.e.,structural motif search combined with neutral loss scanning and metabolite association *** metabolomics analysis was performed on 150 rice cultivars using ultra-performance liquid chromatography coupled with quadrupoleOrbitrap ***,a total of 1939 out of 4491 metabolite features in the MS/MS spectral tag(MS2T)library were annotated,representing an extension of annotation coverage by an order of magnitude in *** differential accumulation patterns of flavonoids between indica and japonica cultivars were revealed,especially O-sulfated flavonoids.A series of closely-related flavonolignans were characterized,adding further evidence for the crucial role of tricin-oligolignols in *** study provides an important protocol for exploring phytochemical diversity in other plant species.

关键词： Untargeted metabolomics MS/MS spectral tag Structural characterization Phytochemical diversity Flavonoid derivative

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Micro-coevolution of host genetics with gut microbiome in three Chinese ethnic groups

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Journal of Genetics and Genomics 2021年第11期48卷 972-983页

作者： Mingyue Cheng Xueling Ge Chaofang Zhong Ruiqing Fu Kang Ning Shuhua Xu Key Laboratory of Molecular Biophysics of the Ministry of Education Hubei Key Laboratory of Bioinformatics and Molecular-imagingCenter of AI BiologyDepartment of Bioinformatics and Systems BiologyCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China State Key Laboratory of Genetic Engineering Center for Evolutionary BiologyCollaborative Innovation Center for Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200438China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Henan Institute of Medical and Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450052China Human Phenome Institute Fudan UniversityShanghai 201203China

Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical *** gain insight into the interactions between host genetic variation and the gut microbiome,we analyzed both the human genome and gut microbiome collected from a cohort of 190 students in the same boarding college and representing 3 ethnic groups,Uyghur,Kazakh,and Han *** found that differences in gut microbiome were greater between genetically distinct ethnic groups than those genetically closely related ones in taxonomic composition,functional composition,enterotype stratification,and microbiome genetic *** also observed considerable correlations between host genetic variants and the abundance of a subset of gut microbial ***,interactions between gut microbiome species and host genetic variants might have coordinated effects on specific human *** ovatus,previously reported to modulate intestinal immunity,is significantly correlated with the host genetic variant rs12899811(meta-P=5.55×10^(-5)),which regulates the VPS33B expression in the colon,acting as a tumor suppressor of colorectal *** results advance our understanding of the micro-coevolution of the human gut microbiome and their interactive effects with host genetic variation on phenotypic diversity.

关键词： Micro-coevolution Gut microbiome Host genetics Uyghur Kazakh Han Chines

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Bioinformatic analysis of lncRNA-associated competing endogenous RNA regulatory networks in synovial tissue of temporomandibular joint osteoarthritis

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BIOCELL 2023年第6期47卷 1293-1306页

作者： CHUYAO WANG CHUAN LU LUXIANG ZOU DONGMEI HE School of Stomatology Qingdao UniversityQingdao266000China Department of Oral Surgery Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyNational Clinical Research Center of StomatologyShanghai200011China

Background:Temporomandibular joint osteoarthritis(TMJOA)is an end-stage disease that seriously affects the patients’quality of *** insights in advancing our understanding of TMJOA are the need of the ***:We performed RNA high-throughput sequencing and bioinformatics analysis of differentially expressed(DE)long non-coding RNA(lncRNAs),microRNAs(miRNAs),and messenger RNA(mRNAs)in human synovial TMJOA ***,synovium samples of TMJOA patients and non-TMJOA controls were collected for highthroughput sequencing of lncRNAs,miRNAs,and *** then performed biological function analysis of the top 100 mRNAs with more than 2-fold differential expression,and their upstream regulated miRNAs and lncRNAs were predicted *** between predicted miRNAs/lncRNAs and differentially expressed miRNAs/lncRNAs were determined,*** networks among the selected lncRNAs,miRNAs,and mRNAs were ***,Western Blotting and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to explore the function of selected lncRNA and ***:Our analysis showed that the only upregulated lncRNAxist,was involved in intracellular protein degradation,cartilage matrix degradation,and osteoclast differentiation through four regulatory axes:miR-1271-5p/ctsb,miR-365a-3p/mmp3,miR-199a-3p/fos,and miR-27b-3p/miR-1271-5p/***-qPCR results showed that xist expression increased in both TMJOA synovial tissue and inflammatory-stimulated synovial *** of xist could promote the proliferation of synovial cells upon inflammatory stimulation,and xist could positively regulate the expression of *** GRB2 could inhibit the expression of matrix degrading enzymes in synovial cells,thereby attenuating the inflammatory ***:Given the current lack of reports of lncRNA regulation in TMJOA synovitis,our results revealed that xist was significantly differentially expressed in human syn

关键词： TMJOA Non-coding RNAs Osteoarthritis prevention and treatment

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MicroRNA-638 inhibits cell proliferation by targeting phospholipase D1 in human gastric carcinoma

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Protein & Cell 2015年第9期6卷 680-688页

作者： Jiwei Zhang Zehua Bian Jialiang Zhou Mingxu Song Zhihui Liu Yuyang Feng Li Zhe Binbin Zhang Yuan Yin Zhaohui Huang Wuxi Oncology Institute The Affiliated Hospital of Jiangnan University Wuxi 214062 China Department of Radiation Oncology The Affiliated Hospital of Jiangnan University Wuxi 214062 China Fudan University shanghai Cancer center and Institutes of Biomedical Sciences Shanghai Medical CollegeFudan University Shanghai 200032 China

MicroRNAs （miRNAs） are a type of small non-coding RNAs that are often play important roles in carcinogene- sis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma （GC）. The expres- sion of miR-638 in GC and the DNA copy number of miR- 638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algo- rithms （TargetScan and miRanda）, luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues （NCTs）, and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Fur- thermore, we observed that PLD1 was overexpressed inGC tissues, and high expression of PLDt in GC predicted poor overall survival. In summary, we revealed that miR- 638 functions as a tumor suppressor in GC through inhibiting PLDI.

关键词： gastric cancer miR-638 cell proliferation,PLD1

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Cistrome Data Browser and Toolkit:analyzing human and mouse genomic data using compendia of ChlP-seq and chromatin accessibility data

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Quantitative Biology 2020年第3期8卷 267-276页

作者： Rongbin Zheng Xin Dong Changxin Wan Xiaoying Shi Xiaoyan Zhang Clifford A.Meyer Clin ical Tran slati onal Research center Shan ghai Pulmonary HospitalSchool of Life Science and Tech no logyTbngji UniversityShanghai 200433China Department of bioinformatics School of Life Science and TechnologyTongji UniversityShanghai 200092China Department of Data Science Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public HealthBostonMA 02215USA center for Functional Cancer Epigenetics Dana-Farber Cancer InstituteBostonMA 02215USA

The Cistrome Data Browser(DB)at the website(***/db)provides about 56,000 published human and mouse ChlP-seq,DNase-seq,and ATAC-seq chromatin profiles,which we have processed using uniform analysis and quality control *** Cistrome DB Toolkit at the website(***)was developed to allow users to investigate fundamental questions using this data *** this tutorial,we describe how to use the Cistrome DB to search for publicly available chromatin profiles,to assess sample quality,to access peak results,to visualize signal intensities,to explore DNA sequence motifs,and to identify putative target genes・We also describe the use of the Toolkit module to seek the factors most likely to regulate a gene of interest,the factors that bind to a given genomic interval(enhancer,SNP,etc.),and samples that have significant peak overlaps with user-defined peak *** tutorial guides biomedical researchers in the use of Cistrome DB resources to rapidly obtain valuable insights into gene regulatory questions.

关键词： ChlP-seq chromatin accessibility gene regulatory analysis transcription factor

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Alternative Polyadenylation： Methods, Findings, and Impacts

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Genomics, Proteomics & bioinformatics 2017年第5期15卷 287-300页

作者： Wei Chen Qi Jia Yifan Song Haihui Fu Gang Wei Ting Ni State Key Laboratory of Genetic Engineering & MOE Key Laboratory of Contemporary Anthropology Collaborative Innovation Center of Genetics and Development School of Life Sciences and Shanghai Cancer Center Fudan University

Alternative polyadenylation （APA）, a phenomenon that RNA molecules with different 3＇ ends originate from distinct polyadenylation sites of a single gene, is emerging as a mechanism widely used to regulate gene expression. In the present review, we first summarized various methods prevalently adopted in APA study, mainly focused on the next-generation sequencing （NGS）-based techniques specially designed for APA identification, the related bioinformatics methods, and the strategies for APA study in single ceils. Then we summarized the main findings and advances so far based on these methods, including the preferences of alternative polyA （pA） site, the biological processes involved, and the corresponding consequences. We especially categorized the APA changes discovered so far and discussed their potential functions under given conditions, along with the possible underlying molecular mechanisms. With more in-depth studies on extensive samples, more signatures and functions of APA will be revealed, and its diverse roles will gradually heave in sight.

关键词： Alternative polyadenylation Next-generation sequencing 3rUTR Alternative splicing Gene regulation

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Insights into the Bamboo Genome:Syntenic Relationships to Rice and Sorghum

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Journal of Integrative Plant Biology 2010年第11期52卷 1008-1015页

作者： Yi-Jie Gui Yan Zhou Yu Wang Sheng Wang Sheng-Yue Wang Yan Hu Shi-Ping Bo Huan Chen Chang-Ping Zhou Nai-Xun Ma Tian-Zhen Zhang Long-Jiang Fan Institute of Crop Science & Institute of bioinformatics Zhejiang UniversityHangzhou 310029China State Key Laboratory of Genetic Engineering Department of MicrobiologySchool of Life SciencesFudan UniversityShanghai 200032China Hangzhou Dianzi University XiashaHangzhou 310018China MOST Key Laboratory of Health and Disease Genomics Chinese National Human Genome Center at ShanghaiShanghai 201203China National Key Laboratory of Crop Genetics and Germplasm Enhancement Nanjing Agriculture UniversityNanjing 210095China Anji Bamboo Exposition Garden Anji 313300China The Research Institute of Subtropical Forestry Chinese Academy of ForestryFuyang 311400China

Bamboo occupies an important phylogenetic node in the grass family and plays a significant role in the forest *** produced 1.2 Mb of tetraploid moso bamboo （Phyllostachys pubescens *** ex *** Leh.） sequences from 13 bacterial artificial chromosome （BAC） clones,and these are the largest genomic sequences available so far from the subfamily *** content of repetitive elements （36.2%） in bamboo is similar to that in *** rice and sorghum exhibit high genomic synteny with bamboo,which suggests that rice and sorghum may be useful as models for decoding Bambusoideae genomes.

关键词： Bamboos Sorghum Rice Genomes

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Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model

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Protein & Cell 2021年第10期12卷 769-787页

作者： Xiaoyan Xu Yaqin Sun Xufeng Cen Bing Shan Qingwei Zhao Tingxue Xie Zhe Wang Tingjun Hou Yu Xue Mengmeng Zhang Di Peng Qiming Sun Cong Yi Ayaz Najafov Hongguang Xia Department of Biochemistry&Research center of Clinical Pharmacy of The First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China Department of Cell Biology Harvard Medical SchoolBostonMA 02115USA Interdisciplinary Research center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201203China College of Pharmaceutical Sciences Hangzhou Institute of innovative MedicineZhejiang UniversityHangzhou 310058China Key Laboratory of Molecular Biophysics of Ministry of Education Hubei Bioinformatics and Molecular Imaging Key LaboratoryCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China

Chaperone-mediated autophagy(CMA)is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative ***,the mechanisms that regulate CMA are not fully ***,using unbiased drug screening approaches,we discover Metformin,a drug that is commonly the first medication prescribed for type 2 diabetes,can induce *** delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA,Hsc70,and its ***,we find that amyloid-beta precursor protein(APP)is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent *** inhibition of CMA-mediated degradation of APP enhances its ***,we find that in the APP/PS1 mouse model of Alzheimer's disease(AD),activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβplaque levels and reverses the molecular and behavioral AD *** study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases,such as AD,where such therapeutic intervention could be beneficial.

关键词： chaperone-mediated autophagy Metformin TAK1 IKKα/β Hsc70 APP Alzheimer’s disease

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Low molecular weight protein phosphatase APH mediates tyrosine dephosphorylation and ABA response in Arabidopsis.

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Stress Biology 2022年第1期2卷 399-410页

作者： Yanyan Du Shaojun Xie Yubei Wang Yu Ma Bei Jia Xue Liu Jingkai Rong Rongxia Li Xiaohong Zhu Chun-Peng Song WAndy Tao Pengcheng Wang shanghai center for Plant Stress Biology CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 200032China bioinformatics Core Purdue UniversityWest LafayetteIN 47907USA University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Crop Stress Adaption and Improvement School of Life SciencesHenan UniversityKaifeng 475004China Department of Biochemistry Purdue UniversityWest LafayetteIN 47907USA

Low molecular weight protein tyrosine phosphatase(LWM-PTP),also known as acid phosphatase,is a highly conserved tyrosine phosphatase in living ***,the function of LWM-PTP homolog has not been reported yet in ***,we revealed a homolog of acid phosphatase,APH,in Arabidopsis plants,is a functional protein tyrosine *** aph mutants are hyposensitive to ABA in post-germination *** performed an anti-phosphotyrosine antibody-based quantitative phosphoproteomics in wild-type and aph mutant and identified hundreds of putative targets of APH,including multiple splicing factors and other transcriptional ***,RNA-seq analysis revealed that the expression of ABA-highly-responsive genes is suppressed in aph ***,APH regulates the ABA-responsive gene expressions by regulating the tyrosine phosphorylation of multiple splicing factors and other post-transcriptional *** also revealed that Tyr383 in RAF9,a member of B2 and B3 RAF kinases that phosphorylate and activate SnRK2s in the ABA signaling pathway,is a direct target site of *** of Tyr383 is essential for RAF9 *** results uncovered a crucial function of APH in ABA-induced tyrosine phosphorylation in Arabidopsis.

关键词： Abscisic acid tyrosine phosphorylaiton phosphatase kinase phosphoproteomics transcriptional regulation RAF SnRK2

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