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生物医学研究杂志:英文版 2023年第5期37卷 367-381页

作者： Ruxu Sun Hongjing Zhu Ying Wang Jianan Wang Chao Jiang Qiuchen Cao Yeran Zhang Yichen Zhang Songtao Yuan Qinghuai Liu Department of Ophthalmology the First Affiliated Hospital of Nanjing Medical UniversityNanjing Medical UniversityNanjingJiangsu 211166China

Age-related macular degeneration(AMD)causes irreversible blindness in people aged over 50 worldwide.The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD.In the current study,we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database.We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis.Peroxisome and tumor necrosis factor-α(TNF-α)signaling and nuclear factor kappa B(NF-κB)were among the top 10 pathways,and thus we selected them to construct AMD cell models to identify differentially expressed Circular RNAs(circrnas).We then constructed a competing endogenous rna network,which is related to differentially expressed circrnas.This network included seven circrnas,15 micrornas,and 82 mrnas.The Kyoto Encyclopedia of Genes and Genomes analysis of mrnas in this network showed that the hypoxia-inducible factor-1(HIF-1)signaling pathway was a common downstream event.The results of the current study may provide insights into the pathological processes of atrophic AMD.

关键词： age-related macular degeneration retinal pigment epithelium Circular RNA bioinformatics analysis competing endogenous rna

Role of Circular RNA expression in the pathological progression after spinal cord injury

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Neural Regeneration Research 2021年第10期16卷 2048-2055页

作者： Wen-Zhao Wang Jun Li Lei Liu Zheng-Dong Zhang Ming-Xin Li Qin Li Hui-Xu Ma Hai Yang Xiao-Ling Hou Department of Orthopedics National Clinical Research Center for GeriatricsWest China HospitalSichuan University/West China School of NursingSichuan UniversityChengduSichuan ProvinceChina

Differential expression of non-coding rna after traumatic spinal cord injury(TSCI)is closely related to the pathophysiological process.The purposes of this study were to systematically profile and characterize expression of Circular RNA(circrna)in the lesion epicenter of spinal tissues after TSCI,and predict the structure and potential function of the regulatory circrna/mirna network.Forty-eight C57BL/6 mice were randomly and equally assigned to two groups:one subjected to TSCI at T8–10 with an Allen’s drop impactor,and a second subjected to laminectomy without TSCI.Spinal cord samples were stained with hematoxylin and eosin,sequenced,and validated.rna-Seq,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and network analyses(Targetscan and miRanda)were used to predict and annotate the circrna/mirna/mrna network.Luciferase reporter,quantitative reverse transcription polymerase chain reaction,and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI.Hematoxylin-eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI.Differentially expressed circrna and mirna profiles were obtained after TSCI;differentially expressed circrnas,which were abundant in the cytoplasm,were involved in positive regulation of transcription and protein phosphorylation.miR-135b-5p was the most significantly downregulated mirna after TSCI;circrnaAbca1 and KLF4 were predicted to be its target circrna and mrna,respectively.Subsequently,the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed,and its targeted binding was verified.After inhibiting circAbca1,GAP43 expression was upregulated.Differential expression of circrnas might play an important role after TSCI.circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis.The identified circrna/mirna/mrna network could provide the basis for understanding pathophysiological mechanisms underlying TSCI,as well as guide the formulation of relate

关键词： bioinformatics circrna/mirna/mrna network Circular RNA gene KLF4 miR-135b-5p spinal cord injury trauma

Antisense oligonucleotide technology can be used to investigate a circular but not linear rna-mediated function for its encoded gene locus

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Science China(Life Sciences) 2021年第5期64卷 784-794页

作者： Zhenxing Song Ruirui Jia Mingfeng Tang Fei Xia Haiyang Xu Zhengguo Li Chuan Huang School of Life Sciences Chongqing UniversityChongqing 400044China Center of Plant Functional Genomics Institute of Advanced Interdisciplinary StudiesChongqing UniversityChongqing 400044China

As a class of powerful molecular tool,antisense oligonucleotides(ASOs)are not only broadly used in protein and rna biology,but also a highly selective therapeutic strategy for many diseases.Although the concept that ASO reagents only reduce expression of the targeted gene in a post-transcriptional manner has long been established,the effect and mechanism of ASO reagents on rna polymerase II(Pol II)transcription are largely unknown.This raised question is particularly important for the appropriate use of ASOs and the valid interpretation of ASO-mediated experiments.In this study,our results show that linear rna ASO attenuates transcription of nascent transcripts by inducing premature transcription termination which is combinatorially controlled by Integrator,exosome,and Rat1 in Drosophila.However,Circular RNA(circrna)ASO transfection does not affect transcription activity of the encoded gene.These data suggest that the ASO technique can be applied to study a circrna-mediated but not linear rna-mediated function for its encoded gene locus.

关键词： antisense oligonucleotide premature transcription termination Circular RNA linear rna

Circular RNA in gastric cancer

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Chinese Medical Journal 2020年第15期133卷 1868-1877页

作者： Xue-Wei Li Wen-Hui Yang Jun Xu Department of Biochemistry and Molecular Biology.Shanxi Medical University TaiyuanShanxi 030001China Cancer Center of Shanxi Bethune Hospital TaiyuanShanxi 030032China Department of Surgery First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China

Gastric cancer(GC)is a common malignancy and is the third leading cause of cancer-related death.At present,there is no simple and effective screening method for early-stage GC,and the treatment results and prognosis are poor.With the continuous improvement of molecular biology techniques,research on Circular RNA(circrna)has gradually expanded over time.Much data supports the role of circrna in tumorigenesis.Moreover,due to its structural specificity and biological stability,circrna is anticipated to be a potential biomarker for tumor diagnosis.Studies have confirmed that circrna can participate in the proliferation,invasion,metastasis,and apoptosis of GC.These findings will lead to novel directions for the diagnosis and treatment of GC.This article reviews the structure and function of circrna,summarizes the current studies on circrna,and discusses the potential diagnostic value of circrna in GC.

关键词： Circular RNA Gastric cancer Biomarker Diagnosis

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

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

Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer

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World Journal of Gastroenterology 2017年第47期23卷 8345-8354页

作者： Fan Yang Dong-Yan Liu Jin-Tao Guo Nan Ge Ping Zhu Xiang Liu Sheng Wang Guo-Xin Wang Si-Yu Sun Endoscopy Center Shengjing Hospital of China Medical University Medical Research Center Shengjing Hospital of China Medical University

AIM To analyze the diagnostic value of a Circular RNA(circR NA), circ-LDLRAD3, in pancreatic cancer.METHODS Expression levels of circ-LDLRAD3 were tested in both cells and clinical samples; the latter included 30 paired pancreatic cancer tissues and adjacent non-tumorous tissues, 31 plasma samples from patients with pancreatic cancer, and 31 plasma samples from healthy volunteers. Real-time quantitative reverse transcriptionpolymerase chain reaction(q RT-PCR) was performed to measure expression levels of circ-LDLRAD3 in cells and clinical samples; then, the relationship between clinicopathological factors of patient samples and expression of circ-LDLRAD3 in pancreatic cancer was analyzed. The diagnostic value of circ-LDLRAD3 was verified by receiver operating characteristic(ROC) curve analysis.RESULTS Circ-LDLRAD3 was up-regulated in pancreatic cancer cell lines(P < 0.01), pancreatic cancer tissues(P < 0.01), and plasma samples from patients with pancreatic cancer(P < 0.01). High expression of circLDLRAD3 was significantly associated with venous invasion, lymphatic invasion, and metastasis. The area under the ROC curve of circ-LDLRAD3 alone or combination with CA19-9 was 0.67 and 0.87, respectively, with a sensitivity and specificity of 0.5738(alone) and 0.7049(alone), and 0.8033(combination) and 0.9355(combination), respectively.CONCLUSION These data suggest that circ-LDLRAD3 may be a biomarker in the diagnosis of pancreatic cancer.

关键词： Circular RNA Pancreatic cancer biomarker

Screening Linear and Circular RNA Transcripts from Stress Granules

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 886-893页

作者： Shuai Chen Jinyang Zhang Fangqing Zhao Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Key Laboratory of Systems Biology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310013China

Stress granules(SGs)are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases.Previous studies have reported the regulatory role of some proteins and linear rnas in SG assembly.However,the relationship between Circular RNAs(circrnas)and SGs has not been discovered.Here,we screened both linear rnas and circrnas in SGs using improved total rna sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs.circrnas with higher SG-related rna-binding protein(RBP)binding abilities are more likely to be enriched in SGs.Furthermore,some SG-enriched circrnas are differentially expressed in hepatocellular carcinoma(HCC)and adjacent tissues.These results suggest the regulatory role of circrnas in SG formation and provide insights into the biological function of circrnas and SGs in HCC.

关键词： Stress granule Circular RNA Protein–rna interaction rna-seq Hepatocellular carcinoma

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

Regulatory rnas,microrna,long-non coding rna and Circular RNA roles in colorectal cancer stem cells

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World Journal of Gastrointestinal Oncology 2022年第4期14卷 748-764页

作者： Hsiao-Mei Chao Teh-Wei Wang Edward Chern Shan-hui Hsu Department of Pathology Wan Fang HospitalTaipei Medical UniversityTaipei 11696Taiwan Department of Pathology School of MedicineCollege of MedicineTaipei Medical UniversityTaipei 110Taiwan niChe Lab for Stem Cell and Regenerative Medicine Department of Biochemical Science and TechnologyNational Taiwan UniversityTaipei 10617Taiwan Institute of Polymer Science and Engineering National Taiwan UniversityTaipei 10617Taiwan

The properties of cancer stem cells(CSCs),such as self-renewal,drug resistance,and metastasis,have been indicated to be responsible for the poor prognosis of patients with colon cancers.The epigenetic regulatory network plays a crucial role in CSC properties.Regulatory non-coding rna(ncrna),including micrornas,long noncoding rnas,and Circular RNAs,have an important influence on cell physiopathology.They modulate cells by regulating gene expression in different ways.This review discusses the basic characteristics and the physiological functions of colorectal cancer(CRC)stem cells.Elucidation of these ncrnas will help us understand the pathological mechanism of CRC progression,and they could become a new target for cancer treatment.

关键词： Regulatory rnas Microrna Long-non coding rna Circular RNA Colorectal cancer Cancer stem cell Stemness