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The circular rna circINPP4B acts as a sponge of miR-30a to regulate Th17 cell differentiation during progression of experimental autoimmune encephalomyelitis

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Cellular & Molecular Immunology 2021年第9期18卷 2177-2187页

作者： Jingjing Han Wei Zhuang Wanhua Feng Fuxing Dong Fang Hua Ruiqin Yao Xuebin Qu Department of Cell Biology and Neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsuChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsuChina Shanghai Key Laboratory of Signaling and Disease Research School of Life Sciences and TechnologyTongji UniversityShanghaiChina Institute of Neurological Diseases of Xuzhou Medical University XuzhouJiangsuChina

circular rnas(circrnas)regulate gene expression and participate in various biological and pathological processes.However,little is known about the effects of specific circrnas on T helper cell 17(Th17)differentiation and related autoimmune diseases,such as multiple sclerosis(MS).Here,using transcriptome microarray analysis at different stages of experimental autoimmune encephalomyelitis(EAE),we identified the EAE progression-related circINPP4B,which showed upregulated expression in Th17 cells from mice with EAE and during Th17 differentiation in vitro.Silencing of circINPP4B inhibited Th17 differentiation and alleviated EAE,characterized by less demyelination and Th17 infiltration in the spinal cord.Mechanistically,circINPP4B served as a sponge that directly targeted miR-30a to regulate Th17 differentiation.Furthermore,circINPP4B levels were associated with the developing phases of clinical relapsing-remitting MS patients.Our results indicate that circINPP4B plays an important role in promoting Th17 differentiation and progression of EAE by targeting miR-30a,which provides a potential diagnostic and therapeutic target for Th17-mediated MS.

关键词： circular rna Multiple sclerosis Experimental autoimmune encephalomyelitis T helper cell miR-30a

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Pro?ling and Validation of the circular rna Repertoire in Adult Murine Hearts

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Genomics, Proteomics & Bioinformatics 2016年第4期14卷 216-223页

作者： Tobias Jakobi Lisa F. Czaja-Hasse Richard Reinhardt Christoph Dieterich Section of Bioinformatics and Systems Cardiology Department of Internal Medicine IIIUniversity Hospital Heidelberg 69120 HeidelbergGermany German Centre for Cardiovascular Research(DZHK) Heidelberg/Mannheim.Germany Max Planck-Genome-Centre Cologne 50829 CologneGermany

For several decades, cardiovascular disease has been the leading cause of death throughout all countries. There is a strong genetic component to many disease subtypes （e.g., cardiomyopa- thy） and we are just beginning to understand the relevant genetic factors. Several studies have related rna splicing to cardiovascular disease and circular rnas （circrnas） are an emerging player, circrnas, which originate through back-splicing events from primary transcripts, are resis- tant to exonucleases and typically not polyadenylated. Initial functional studies show clear phenotypic outcomes for selected circrnas. We provide, for the first time, a comprehensive catalogue of rnase R-resistant circrna species for the adult murine heart. This work combines state-of-the-art circle sequencing with our novel DCC software to explore the circrna landscape of heart tissue. Overall, we identified 575 circrna species that pass a beta-binomial test for enrichment （false discovery rate of 1%） in the exonuclease-treated sequencing sample. Several circrnas can be directly attributed to host genes that have been previously described as associated with cardiovascular disease. Further studies of these candidate circrnas may reveal disease-relevant properties or functions of specific circrnas.

关键词： circular rna circSeq Cardiovascular disease Cardiomyopathy Computational cardiology

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Novel circular rna expression profile of uveal melanoma revealed by microarray

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Chinese Journal of Cancer Research 2018年第6期30卷 656-668页

作者： Xuan Yang Yang Li Yueming Liu Xiaolin Xu Yingzhi Wang Yanni Yan Wenjia Zhou Jingyan Yang Wenbin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology & Visual Sciences Key LabBeijing Tongren HospitalCapital Medical University Beijing Institute of Ophthalmology Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology & Visual Sciences Key Laboratory

Objective: The present study aimed to investigate circular rna(circrna) expression in uveal melanoma(UM).Methods: First,we used microarray to compare the expression profiles of circrna in five UM samples and five normal uvea tissues.Next,bioinformatics analyses,including gene ontology(GO) analysis and pathway analysis,were applied to study these differentially expressed circrnas to predict pathogenic pathways that may be involved.Quantitative real-time polymerase chain reaction(qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circrna expression profiles obtained from the microarray data.Finally,we analyzed the interaction between validated circrnas and their potential cancer-associated mirna targets.Results: In total,50,579 circrnas [fold change(FC) ≥2.0; Prnas,were identified as differentially expressed between UM tissues and normal uvea tissues.We used qRT-PCR to verify seven dysregulated circrnas indicated by the microarray data,including hsacirc0119873,hsacirc0128533,hsacirc0047924,hsacirc0103232,hsa-circrna10628-6,hsacirc0032148 and hsacirc0133460,which may be promising candidates to study future molecular mechanisms.Conclusions: This study explored,for the first time,the abnormal expression of circrnas in UM and described the expression profile of circrnas,providing a new potential target for the mechanism of UM and future treatment of UM.

关键词： Uveal melanoma circular rna microarray noncoding rna

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circular rna and its potential as prostate cancer biomarkers

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World Journal of Clinical Oncology 2020年第8期11卷 563-572页

作者： Dwayne Tucker Wei Zheng Da-Hong Zhang Xuesen Dong Department of Urologic Sciences University of British ColumbiaVancouverBC V6H 3Z6Canada Department of Urology Zhejiang Provincial People's HospitalHangzhou 310024Zhejiang ProvinceChina

Advancing knowledge of the transcriptome has revealed that circular rnas(circrnas)are widely expressed and evolutionarily conserved molecules that may serve relevant biological roles.More interesting is the accumulating evidence which demonstrates the implication of circrnas in diseases,especially cancers.This revelation has helped to form the rationale for many studies exploring their utility as clinical biomarkers.Circrnas are highly stable due to their unique structures,exhibit some tissue specificity,and are enriched in exosomes,which facilitate their detection in a range of body fluids.These properties make circrnas ideal candidates for biomarker development in many diseases.This review will outline the discovery,biogenesis,and proposed functions of circrnas.

关键词： circular rna rna splicing Prostate cancer Biomarker Cell-free rna

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circular rnas:typical biomarkers for bone-related diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第12期23卷 975-988页

作者： Linghui HU Wei WU Jun ZOU School of Exercise and Health Shanghai University of SportShanghai 200438China

Bone is a connective tissue that has important functions in the human body.Cells and the extracellular matrix(ECM)are key components of bone and are closely related to bone-related diseases.However,the outcomes of conventional treatments for bone-related diseases are not promising,and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy.circular rnas(circrnas)are single-stranded rnas that form closed circular structures without a 5’cap or 3’tail and polycyclic adenylate tails.Due to their high stability,circrnas have the potential to be typical biomarkers.Accumulating evidence suggests that circrnas are involved in bone-related diseases,including osteoarthritis,osteoporosis,osteosarcoma,multiple myeloma,intervertebral disc degeneration,and rheumatoid arthritis.Herein,we summarize the recent research progress on the characteristics and functions of circrnas,and highlight the regulatory mechanism of circrnas in bone-related diseases.

关键词： circular rna Bone-related disease Competing endogenous rna(cerna) Microrna

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rtcisE2F promotes the self-renewal and metastasis of liver tumorinitiating cells via N^(6)-methyladenosine-dependent E2F3/E2F6 mrna stability

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Science China(Life Sciences) 2022年第9期65卷 1840-1854页

作者： Zhenzhen Chen Lan Huang Kaili Wang Lulu Zhang Xiang Zhong Zhongyi Yan Benyu Liu Pingping Zhu School of Life Sciences Zhengzhou UniversityZhengzhou 450001China Biotherapy Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China School of Basic Medical Sciences Henan UniversityKaifeng 475004China Research Center of Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhou 450052China

Liver cancer is highly heterogeneous,and the tumor tissue harbors a variety of cell types.Liver tumor initiating cells(TICs)well contribute to tumor heterogeneity and account for tumor initiation and metastasis,but the molecular mechanisms of liver TIC self-renewal are elusive.Here,we identified a functional read-through rt-circrna,termed rtcisE2F,that is highly expressed in liver cancer and liver TICs.rtcisE2F plays essential roles in the self-renewal and activities of liver TICs.rtcisE2F targets E2F6 and E2F3 mrnas,attenuates mrna turnover,and increases E2F6/E2F3 expression.Mechanistically,rtcisE2F functions as a scaffold of N^(6)-methyladenosine(m^(6)A)reader IGF2BP2 and E2F6/E2F3 mrna.rtcisE2F promotes the association of E2F6/E2F3 mrnas with IGF2BP2,and inhibits their association with another m^(6)A reader,YTHDF2.IGF2BP2 inhibits E2F6/E2F3 mrna decay,whereas YTHDF2 promotes E2F6/E2F3 mrna decay.By switching m^(6)A readers,rtcisE2F enhances E2F6/E2F3 mrna stability.E2F6 and E2F3 are both required for liver TIC self-renewal and Wnt/β-catenin activation,and inhibition of these pathways is a potential strategy for preventing liver tumorigenesis and metastasis.In conclusion,the rtcisE2F-IGF2BP2/YTHDF2-E2F6/E2F3-Wnt/β-catenin axis drives liver TIC self-renewal and initiates liver tumorigenesis and metastasis,and may provide a strategy to eliminate liver TICs.

关键词： circular rna tumor-initiating cells self-renewal metastasis N^(6)-methyladenosine

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circPTPN4 regulates myogenesis via the miR-499-3p/NAMPT axis

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Journal of Animal Science and Biotechnology 2022年第3期13卷 682-696页

作者： Bolin Cai Manting Ma Zhen Zhou Shaofen Kong Jing Zhang Xiquan Zhang Qinghua Nie State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Lingnan Guangdong Laboratory of AgricultureCollege of Animal ScienceSouth China Agricultural UniversityGuangzhou 510642GuangdongChina Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Laboratory of Chicken GeneticsBreeding and ReproductionMinistry of AgricultureGuangzhou 510642GuangdongChina

Background:circular rnas(circ rnas)are a novel class of endogenous nc rna,which widely exist in the transcriptomes of different species and tissues.Recent studies indicate important roles for circ rnas in the regulation of gene expression by acting as competing endogenous rnas(ce rnas).However,the specific role of circ rnas in myogenesis is still poorly understood.In this study,we attempted to systematically identify the circ rnas involved in myogenesis and analyze the biological functions of circ rnas in chicken skeletal muscle development.Results:In total,532 circ rnas were identified as being differentially expressed between pectoralis major(PEM)and soleus(SOL)in 7-week-old Xinghua chicken.Among them,a novel circ rna(novel_circ_002621),generated by PTPN4 gene,was named circ PTPN4 and identified.circ PTPN4 is highly expressed in skeletal muscle,and its expression level is upregulated during myoblast differentiation.circ PTPN4 facilitates the proliferation and differentiation of myoblast.Moreover,circ PTPN4 suppresses mitochondria biogenesis and activates fast-twitch muscle phenotype.Mechanistically,circ PTPN4 can function as a ce rna to regulate NAMPT expression by sponging mi R-499-3p,thus participating in AMPK signaling.Conclusions:circ PTPN4 functions as a ce rna to regulate NAMPT expression by sponging mi R-499-3p,thus promoting the proliferation and differentiation of myoblast,as well as activating fast-twitch muscle phenotype.

关键词： Chicken Circ PTPN4 circular rna MiR-499-3p Myogenesis NAMPT The transformation of myofiber

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Dynamic rna profiles in the small intestinal epithelia of cats after Toxoplasma gondii infection

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Infectious Diseases of Poverty 2023年第4期12卷 63-82页

作者： Bintao Zhai Shi-Chen Xie Jiyu Zhang Jun-Jun He Xing-Quan Zhu Key Laboratory of Veterinary Pharmaceutical Development Ministry of Agriculture and Rural AffairsLanzhou Institute of Husbandry and Pharmaceutical SciencesChinese Academy of Agricultural SciencesLanzhou730050GansuPeople’s Republic of China State Key Laboratory for Animal Disease Control and Prevention Key Laboratory of Veterinary Parasitology of Gansu ProvinceLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046GansuPeople’s Republic of China Laboratory of Parasitic Diseases College of Veterinary MedicineShanxi Agricultural UniversityTaigu030801ShanxiPeople’s Republic of China Research Center for Parasites&Vectors College of Veterinary MedicineHunan Agricultural UniversityChangsha410128HunanPeople’s Republic of China Key Laboratory of Veterinary Public Health of Yunnan Province College of Veterinary MedicineYunnan Agricultural UniversityKunming650201YunnanPeople’s Republic of China

Background Felids are the only definitive hosts ofToxoplasma gondii. However, the biological features of the feline small intestine followingT. gondii infection are poorly understood. We investigated the changes in the expression of rnas (including mrnas, long non-coding rnas and circular rnas) in the small intestinal epithelia of cats followingT. gondii infection to improve our understanding of the life cycle ofT. gondii and cat responses toT. gondii infection.Methods Fifteen cats were randomly assigned to five groups, and the infection groups were inoculated with 600 tissue cysts of theT. gondii Pru strain by gavage. The small intestinal epithelia of cats were collected at 6, 10, 14, and 30 days post infection (DPI). Using high-throughput rna sequencing (rna-seq), we investigated the changes in rna expression. The expression levels of differentially expressed (DE) genes and non-coding rnas (ncrnas) identified by rna-seq were validated by quantitative reverse transcription PCR (qRT-PCR). Differential expression was determined using the DESeq R package.Results In total, 207 annotated lncrnas, 20,552 novel lncrnas, 3342 novel circrnas and 19,409 mrnas were identified. Among these, 70 to 344 DE mrnas, lncrnas and circrnas were detected, and the post-cleavage binding sites between 725 ncrnas and 2082 mirnas were predicted. Using the co-location method, we predicted that a total of 235 lncrnas target 1044 protein-coding genes, while the results of co-expression analysis revealed that 174 lncrnas target 2097 mrnas. Pathway enrichment analyses of the genes targeted by ncrnas suggested that most ncrnas were significantly enriched in immune or diseases-related pathways. Ncrna regulatory networks revealed that a single ncrna could be directly or indirectly regulated by multiple genes or ncrnas that could influence the immune response of cats. Co-expression analysis showed that 242 circrnas, mainly involved in immune responses, were significantly associated withT. gondii infection. In contrast, 1352 protein coding rnas, ma

关键词： Toxoplasma gondii Definitive host Cat Small intestinal epithelia Long non-coding rna circular rna mrna

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Critical involvement of circular rnas in virus-associated cancers

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Genes & Diseases 2023年第6期10卷 2296-2305页

作者： Arghavan Zebardast Tayebeh Latifi Moein shirzad Golnaz Goodarzi Saeed Ebrahimi Fana Sadra Samavarchi Tehrani Yousef Yahyapour Department of Virology School of Public HealthTehran University of Medical SciencesTehran ***Iran Cellular and Molecular Biology Research Center Health Research InstituteBabol University of Medical SciencesBabol 47176Iran Department of Clinical Biochemistry School of MedicineTehran University of Medical SciencesTehran ***Iran Student Scientific Research Center Tehran University of Medical SciencesTehran ***Iran Infectious Diseases and Tropical Medicine Research Center Health Research InstituteBabol University of Medical SciencesBabol 47176Iran

Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV), Epstein–Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus (HTLV), and Merkel cell polyomavirus (MCV)) that infect humans have been identified as an oncogene and have been associated with several human malignancies. Recently, growing attention has been attracted to exploring the pathogenesis of virus-related cancers. One of the most mysterious molecules involved in carcinogenesis and progression of virus-related cancers is circular rnas (circrna). These emerging non-coding rnas (ncrnas), due to the absence of 5′ and 3′ ends, have high stability than linear rnas and are found in some species across the eukaryotic organisms. Compelling evidence has revealed that viruses also encode a repertoire of circrnas, as well as dysregulation of these viral circrnas play a critical role in the pathogenesis and progression of different types of virus-related cancers. Therefore, understanding the exact role and function of the virally encoded circrnas with virus-associated cancers will open a new road for increasing our knowledge about the rna world. Hence, in this review, we will focus on emerging roles of virus-encoded circrnas in multiple cancers, including cervical cancer, gastric cancer, Merkel cell carcinoma, nasopharyngeal carcinoma, Kaposi cancer, and liver cancer.

关键词： Cancer circular rna Neoplasms Oncogenes Viruses

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Regulation of Glial Function by Noncoding rna in Central Nervous System Disease

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Neuroscience Bulletin 2023年第3期39卷 440-452页

作者： Ying Bai Hui Ren Liang Bian You Zhou Xinping Wang Zhongli Xiong Ziqi Liu Bing Han Honghong Yao Department of Pharmacology Jiangsu Provincial Key LaboratorySchool of MedicineSoutheast UniversityNanjing 210009China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute of Life Sciences Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210009China

Non-coding rnas(ncrnas)are a class of functional rnas that play critical roles in different diseases.Ncrnas include micrornas,long ncrnas,and circular rnas.They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system(CNS)diseases.Mounting evidence indicates that ncrnas play key roles in CNS diseases.Further elucidating the mechanisms of ncrna underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.

关键词： Noncoding rna Microrna Long noncoding rna circular rna Astrocytes Microglia Oligodendrocytes

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