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circular rnas:Diagnostic and Therapeutic Perspectives in CNS Diseases

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Current Medical Science 2023年第5期43卷 879-889页

作者： Ying BAI Hong-hong YAO Jiangsu Provincial Key Laboratory of Critical Care Medicine Department of PharmacologySchool 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

circular rnas(circrnas)are a class of regulatory non-coding rnas characterized by the presence of covalently closed ends.A growing body of evidence suggests that circrnas play important roles in physiology and pathology.In particular,accumulating data on circRNA functions in various central nervous system(CNS)diseases and their correlations indicate that circrnas are critical contributors to the onset and development of brain disorders.In this review,we focus on the regulatory and functional roles of circrnas in CNS diseases,highlighting their diagnostic and therapeutic potential,with the aim of providing new insights into CNS diseases.

关键词： circular rnas brain central nervous system disease diagnosis therapy

circular rnas in pulmonary hypertension:Emerging biological concepts and potential mechanism

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Animal Models and Experimental Medicine 2022年第1期5卷 38-47页

作者： Qian Wang Yuanyuan Sun Qinhua Zhao Wenhui Wu Lan Wang Yuqing Miao Ping Yuan Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and Technology

circular rnas(circrnas)are endogenous rnas with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circrnas have been identified and further functional studies have been performed.It is known that circrnas act as potential biomarkers,sponges for micrornas(mirnas)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circrnas are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circrnas can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circrnas are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circrnas in the pathogenesis of PH.

关键词： biological characterization circular rnas miRNA sponges pulmonary hypertension

The biogenesis,function and clinical significance of circular rnas in breast cancer

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Cancer Biology & Medicine 2022年第1期19卷 14-29页

作者： Yan Zeng Yutian Zou Guanfeng Gao Shaoquan Zheng Song Wu Xiaoming Xie Hailin Tang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China

circular rnas(circ rnas)are noncoding rnas that form covalently closed loop structures.Circ rnas are dysregulated in cancer and play key roles in tumorigenesis,diagnosis,and tumor therapy.Circ rnas function as competing endogenous rnas or micro RNA sponges that regulate transcription and splicing,binding to proteins,and translation.Circ rnas may serve as novel biomarkers for cancer diagnosis,and they show potential as therapeutic targets in cancers including breast cancer(BC).In women,BC is the most common malignant tumor worldwide and the second leading cause of cancer death.Although evidence indicates that circ rnas play a critical role in BC,the mechanisms regulating the function of circ rnas in BC remain poorly understood.Here,we provide literature review aiming to clarify the role of circ rnas in BC and summarize the latest research.We provide a systematic overview of the biogenesis and biological functions of circ rnas,elaborate on the functional roles of circ rnas in BC,and highlight the value of circ rnas as diagnostic and therapeutic targets in BC.

关键词： Breast cancer circular rnas carcinogenesis tumor biomarker targeted therapy

Biological functions and potential implications of circular rnas

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The Journal of Biomedical Research 2023年第2期37卷 89-99页

作者： Lan Ma Haiyan Chu Meilin Wang Zhengdong Zhang Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China.

circular rnas(circrnas) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circrnas play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges,interacting with proteins, modulating the expression of related genes and translating into peptides or proteins.Circrnas have also been used as biomarkers for a number of diseases, which could improve clinical practice.This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circrnas as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circrnas to facilitate their clinical transformation into disease treatment.

关键词： circular rnas biogenesis mechanisms database biomarkers

RNA-Seq profiling of circular rnas in human colorectal cancer 5-fluorouracil resistance and potential biomarkers

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 678-689页

作者： Pei-Qiu Cheng Yu-Jing Liu Sheng-An Zhang Lu Lu Wen-Jun Zhou Dan Hu Han-Chen Xu Guang Ji Institute of Digestive Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Shanghai University of Traditional Chinese Medicine Shanghai 200032China Shanghai Pudong New Area Hospital of Traditional Chinese Medicine Shanghai 200032China

BACKGROUND Colorectal cancer(CRC)is a commonly diagnosed cancer of the digestive system worldwide.Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment,drug resistance is a problem that cannot be ignored and needs to be solved.AIM To explore the relationship between circular RNA(circRNA)and CRC drug resistance.circRNA plays a key role in the occurrence and development of cancers,but its function in the process of drug resistance has not been widely revealed.METHODS To explore the role of circRNA in 5-fluorouracil(5-Fu)resistance,we performed the circRNA expression profile in two CRC cell lines and their homologous 5-Fu resistant cells by high-throughput sequencing.RESULTS We validated the differentially expressed circrnas in other two paired CRC cells,confirmed that circ_0002813 and circ_0000236 could have a potential competitive endogenous RNA mechanism and be involved in the formation of 5-Fu resistance.And we combined the sequencing results of mRNA to construct the regulatory network of circRNA-miRNA-mRNA.CONCLUSION Our study revealed that circ_0002813 and circ_0000236 may as the biomarkers to predict the occurrence of 5-Fu resistance in CRC.

关键词： Colorectal cancer 5-Fluorouracil resistance circular rnas RNA sequencing Network prediction Biomarkers

Advancements in our understanding of circular and long non-coding rnas in spinal cord injury

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Neural Regeneration Research 2022年第11期17卷 2399-2403页

作者： Yan Zhang Ho Jun Yun Yu Ji Eric Cosky Wen-Xiu Zhang Wei Han Yu-Chuan Ding Central Laboratory Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Neurosurgery Wayne State University School of MedicineDetroitMIUSA Department of General Surgery Beijing Luhe HospitalCapital Medical UniversityBeijingChina

Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding rnas,including both long non-coding rnas(lncrnas)and circular rnas(circrnas),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncrnas and circrnas in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncrnas and circrnas are novel modulato rs of SCI pathogenesis will be discussed.

关键词： circular rnas function long non-coding rnas neuronal cells neuronal glia pathogenesis regulation spinal cord injury

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

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Animal Models and Experimental Medicine 2024年第3期7卷 310-323页

作者： Xiaoyi Hu Shang Wang Hui Zhao Yaqin Wei Ruowang Duan Rong Jiang Wenhui Wu Qinhua Zhao Sugang Gong Lan Wang Jinming Liu Ping Yuan Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of Geriatrics Shanghai Institute of GeriatricsHuadong HospitalFudan UniversityShanghaiChina Department of Anesthesiology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Background:circular rnas(circrnas)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circrnas in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circrnas and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circrnas in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circrnas under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

关键词： circular postmeiotic segregation 1 circular rnas hypoxia pulmonary hypertension vascular cells

Construction of the underlying circRNA-miRNA-mRNA regulatory network and a new diagnostic model in ulcerative colitis by bioinformatics analysis

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World Journal of Clinical Cases 2024年第9期12卷 1606-1621页

作者： Yu-Yi Yuan Hui Wu Qian-Yun Chen Heng Fan Bo Shuai Department of Integrated Traditional Chinese and Western Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022Hubei ProvinceChina

BACKGROUND circular rnas(circrnas)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circrnas in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circrnas,mirnas,and mrnas in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circrnas.We identified the most relevant differential circrnas for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circrnas,three mirnas,and 38 mrnas.Two optimal prognostic-related differentially expressed circrnas,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.

关键词： circular rnas RNA regulatory network Ulcerative colitis New predictive model Bioinformatics Diagnose

CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression

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Oncology Research 2024年第6期32卷 1129-1139页

作者： JUNZHE YI BINBIN LI XIAOMIN YIN LINGRUI LIU CAILU SONG YING ZHAO MANBO CAI HAILIN TANG DONG CHEN NING LYU State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Medical Oncology The Third People’s Hospital of YongzhouYongzhou425000China Department of Radiotherapy The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang421001China Center of Hepato-Pancreato-Biliary Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China

circular rnas(circrnas)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circrnas in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.

关键词： circular rnas circMYBL2 miR-1205 E2F1 Hepatocellular carcinoma