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Wang M, Zheng S, Zhang Y, Zhang J, Lai F, Zhou C, Zhou Q, Li X, Li G. Transcriptome analysis reveals PTBP1 as a key regulator of circRNA biogenesis. BMC Biol 2025; 23:127. [PMID: 40350413 PMCID: PMC12067716 DOI: 10.1186/s12915-025-02233-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 05/02/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are a class of non-coding RNAs generated through back splicing. High expression of circRNAs is often associated with numerous abnormal cellular biological processes. However, the regulatory factors of circRNAs are not fully understood. RESULTS In this study, we identified PTBP1 as a crucial regulator of circRNA biogenesis through a comprehensive analysis of the whole transcriptome profiles across 10 diverse cell lines. Knockdown of PTBP1 led to a significant decrease in circRNA expression, concomitant with a distinct reduction in cell proliferation. To investigate the regulatory mechanism of PTBP1 on circRNA biogenesis, we constructed a minigene reporter based on SPPL3 gene. The results showed that PTBP1 can bind to the flanking introns of circSPPL3, and the mutation of PTBP1 motif impedes the back splicing of circSPPL3. Subsequently, to demonstrate that this observation is not an exception, the comprehensive regulatory effects of PTBP1 on circRNAs were confirmed by miniGFP, reflecting the necessity of the binding site in the flanking introns. Analysis of data from clinical samples showed that both PTBP1 and circRNAs exhibited substantial upregulation in acute myeloid leukemia, further demonstrating a potential role for PTBP1 in promoting circRNA biogenesis under in vivo conditions. Competitive endogenous RNA (ceRNA) network revealed that PTBP1-associated circRNAs participated in biological processes associated with cell proliferation. CONCLUSIONS In summary, our study is the first to identify the regulatory effect of PTBP1 on circRNA biogenesis and indicates a possible link between PTBP1 and circRNA expression in leukemia.
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Affiliation(s)
- Mohan Wang
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Shanshan Zheng
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yan Zhang
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Jingwen Zhang
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Fuming Lai
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Cong Zhou
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Qiangwei Zhou
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
| | - Xingwang Li
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
| | - Guoliang Li
- National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China.
- Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China.
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An Q, Cao Y, Guo W, Jiang Z, Luo H, Liu H, Zhan X. Identification of common genes of rhinovirus single/double‑stranded RNA‑induced asthma deterioration by bioinformatics analysis. Exp Ther Med 2024; 27:210. [PMID: 38590566 PMCID: PMC11000450 DOI: 10.3892/etm.2024.12498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/29/2024] [Indexed: 04/10/2024] Open
Abstract
Rhinovirus (RV) is the most common respiratory virus affecting humans. The majority of asthma deteriorations are triggered by RV infections. However, whether the effects of RV single- and double-stranded RNA on asthma deterioration have common target genes needs to be further studied. In the present study, two datasets (GSE51392 and GSE30326) were used to screen for common differentially expressed genes (cDEGs). The molecular function, signaling pathways, interaction networks, hub genes, key modules and regulatory molecules of cDEGs were systematically analyzed using online tools such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, STRING and NetworkAnalyst. Finally, the hub genes STAT1 and IFIH1 were verified in clinical samples using reverse transcription-quantitative PCR (RT-qPCR). A total of 85 cDEGs were identified. Function analysis revealed that cDEGs served an important role in the innate immune response to viruses and its regulation. Signal transducer and activator of transcription 1 (STAT1), interferon induced with helicase C domain 1 (IFIH1), interferon regulatory factor 7 (IRF7), DExD/H box helicase 58 (DDX58) and interferon-stimulating gene 15 (ISG15) were detected to be hub genes based on the protein-protein interactions and six topological algorithms. A key module involved in influenza A, the Toll-like receptor signaling pathway, was identified using Cytoscape software. The hub genes were regulated by GATA-binding factor 2 and microRNA-146a-5p. In addition, RT-qPCR indicated that the expression levels of the hub genes STAT1 and IFIH1 were low during asthma deterioration compared with post-treatment recovery samples. The present study enhanced the understanding of the mechanism of RV-induced asthma deterioration.
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Affiliation(s)
- Qian An
- Department of Respiratory and Critical Care Medicine, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, Anhui 241000, P.R. China
| | - Yi Cao
- Department of Medical Parasitology, School of Basic Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Wei Guo
- Department of Medical Parasitology, School of Basic Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Ziyun Jiang
- Department of Medical Parasitology, School of Basic Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Hui Luo
- Department of Medical Parasitology, School of Basic Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Hui Liu
- Department of Medical Parasitology, School of Basic Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
| | - Xiaodong Zhan
- Department of Medical Parasitology, School of Basic Medicine, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
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Kang L, Xie H, Ye H, Jeyarajan AJ, Warner CA, Huang Y, Shi Y, Li Y, Yang C, Xu M, Lin W, Sun J, Chen L, Duan X, Li S. Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway. J Virol 2023; 97:e0123223. [PMID: 38051045 PMCID: PMC10734422 DOI: 10.1128/jvi.01232-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 11/13/2023] [Indexed: 12/07/2023] Open
Abstract
IMPORTANCE Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.
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Affiliation(s)
- Lan Kang
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
- Chengdu Fifth People’s Hospital, Chengdu, Sichuan, China
| | - He Xie
- The Hospital of Xidian Group, Xian, Shaanxi, China
| | - Haiyan Ye
- Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu, Sichuan, China
| | - Andre J. Jeyarajan
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Charlotte A. Warner
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Yike Huang
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
| | - Yaoqiang Shi
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
| | - Yujia Li
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
| | - Chunhui Yang
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
| | - Min Xu
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
| | - Wenyu Lin
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jujun Sun
- The Hospital of Xidian Group, Xian, Shaanxi, China
| | - Limin Chen
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
- The Hospital of Xidian Group, Xian, Shaanxi, China
- Joint Laboratory on Transfusion-transmitted Infectious Diseases between Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Nanning Blood Center, Nanning Blood Center, Key Laboratory for Transfusion-transmitted Infectious Diseases of the Health Commission of Nanning City, Nanning, Guangxi, China
| | - Xiaoqiong Duan
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Shilin Li
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China
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Weidle UH, Nopora A. Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in Preclinical In Vivo Models. Cancer Genomics Proteomics 2023; 20:500-521. [PMID: 37889063 PMCID: PMC10614070 DOI: 10.21873/cgp.20401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/22/2023] [Accepted: 08/30/2023] [Indexed: 10/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranges as number two with respect to the incidence of tumors and is associated with a dismal prognosis. The therapeutic efficacy of approved multi-tyrosine kinase inhibitors and checkpoint inhibitors is modest. Therefore, the identification of new therapeutic targets and entities is of paramount importance. We searched the literature for up-regulated circular RNAs (circRNAs) which mediate efficacy in preclinical in vivo models of HCC. Our search resulted in 14 circRNAs which up-regulate plasma membrane transmembrane receptors, while 5 circRNAs induced secreted proteins. Two circRNAs facilitated replication of Hepatitis B or C viruses. Three circRNAs up-regulated high mobility group proteins. Six circRNAs regulated components of the ubiquitin system. Seven circRNAs induced GTPases of the family of ras-associated binding proteins (RABs). Three circRNAs induced redox-related proteins, eight of them up-regulated metabolic enzymes and nine circRNAs induced signaling-related proteins. The identified circRNAs up-regulate the corresponding targets by sponging microRNAs. Identified circRNAs and their targets have to be validated by standard criteria of preclinical drug development. Identified targets can potentially be inhibited by small molecules or antibody-based moieties and circRNAs can be inhibited by small-interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) for therapeutic purposes.
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Affiliation(s)
- Ulrich H Weidle
- Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
| | - Adam Nopora
- Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
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Xie H, Huang Y, Zhan Y. Construction of a novel circRNA-miRNA-ferroptosis related mRNA network in ischemic stroke. Sci Rep 2023; 13:15077. [PMID: 37699956 PMCID: PMC10497552 DOI: 10.1038/s41598-023-41028-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 08/21/2023] [Indexed: 09/14/2023] Open
Abstract
Molecule alterations are important to explore the pathological mechanism of ischemic stroke (IS). Ferroptosis, a newly recognized type of regulated cell death, is related to IS. Identification of the interactions between circular RNA (circRNA), microRNA (miRNA) and ferroptosis related mRNA may be useful to understand the molecular mechanism of IS. The circRNA, miRNA and mRNA transcriptome data in IS, downloaded from the Gene Expression Omnibus (GEO) database, was used for differential expression analysis. Ferroptosis related mRNAs were identified from the FerrDb database, followed by construction of circRNA-miRNA-ferroptosis related mRNA network. Enrichment and protein-protein interaction analysis of mRNAs in circRNA-miRNA-mRNA network was performed, followed by expression validation by reverse transcriptase polymerase chain reaction and online dataset. A total of 694, 41 and 104 differentially expressed circRNAs, miRNAs and mRNAs were respectively identified in IS. Among which, dual specificity phosphatase 1 (DUSP1), nuclear receptor coactivator 4 (NCOA4) and solute carrier family 2 member 3 (SLC2A3) were the only three up-regulated ferroptosis related mRNAs. Moreover, DUSP1, NCOA4 and SLC2A3 were significantly up-regulated in IS after 3, 5 and 24 h of the attack. Based on these three ferroptosis related mRNAs, 4 circRNA-miRNA-ferroptosis related mRNA regulatory relationship pairs were identified in IS, including hsa_circ_0071036/hsa_circ_0039365/hsa_circ_0079347/hsa_circ_0008857-hsa-miR-122-5p-DUSP1, hsa_circ_0067717/hsa_circ_0003956/hsa_circ_0013729-hsa-miR-4446-3p-SLC2A3, hsa_circ_0059347/hsa_circ_0001414/hsa_circ_0049637-hsa-miR-885-3p-SLC2A3, and hsa_circ_0005633/hsa_circ_0004479-hsa-miR-4435-NCOA4. In addition, DUSP1 is involved in the signaling pathway of fluid shear stress and atherosclerosis. Relationship of regulatory action between circRNAs, miRNAs and ferroptosis related mRNAs may be associated with the development of IS.
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Affiliation(s)
- Huirong Xie
- Department of Neurology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Clinical Research Center for Neurological Diseases, 289 Kuocang Road, Lishui, 323000, Zhejiang, China.
| | - Yijie Huang
- Department of Neurology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Clinical Research Center for Neurological Diseases, 289 Kuocang Road, Lishui, 323000, Zhejiang, China
| | - Yanli Zhan
- Cerebrovascular Research Laboratory, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Clinical Research Center for Neurological Diseases, 289 Kuocang Road, Lishui, 323000, Zhejiang, China
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Zhang MH, Yuan YF, Liu LJ, Wei YX, Yin WY, Zheng LZY, Tang YY, Lv Z, Zhu F. Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:4706-4735. [PMID: 37664153 PMCID: PMC10473924 DOI: 10.3748/wjg.v29.i31.4706] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/29/2023] [Accepted: 08/01/2023] [Indexed: 08/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignancy with a high incidence and fatality rate worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for its occurrence and development. Early detection of HBV-associated HCC (HBV-HCC) can improve clinical decision-making and patient outcomes. Biomarkers are extremely helpful, not only for early diagnosis, but also for the development of therapeutics. MicroRNAs (miRNAs), a subset of non-coding RNAs approximately 22 nucleotides in length, have increasingly attracted scientists' attention due to their potential utility as biomarkers for cancer detection and therapy. HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis. In this review, we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC. From a molecular standpoint, we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC. In the near future, miRNA-based diagnostic, prognostic, and therapeutic applications will make their way into the clinical routine.
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Affiliation(s)
- Ming-He Zhang
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yu-Feng Yuan
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Li-Juan Liu
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yu-Xin Wei
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Wan-Yue Yin
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Lan-Zhuo-Yin Zheng
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Ying-Ying Tang
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Zhao Lv
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Fan Zhu
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Hubei Province Key Laboratory of Allergy & Immunology, Wuhan University, Wuhan 430071, Hubei Province, China
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Shi J, Rui X, Han C, Wang C, Xu L, Jiang X. circRNF13, a novel N 6-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability. Cell Death Discov 2023; 9:253. [PMID: 37468464 DOI: 10.1038/s41420-023-01557-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) and N6-methyladenosine (m6A) have been shown to play an increasingly critical role in the development of different cancers. However, there is limited evidence on how circRNAs and m6A interact to affect the radiosensitivity of cervical cancer (CC). This study provides a mechanistic understanding of the novel m6A-regulated circRNF13 in enhancing radioresistance in CC. METHODS Differentially expressed circRNAs were identified from radiosensitive and radioresistant CC tissues. Meanwhile, these circRNAs were subjected to methylated RNA immunoprecipitation (Me-RIP). Finally, the effects of these circRNAs on radiosensitivity were characterized. RESULTS CircRNF13 was poorly expressed in CC patients that were sensitive to concurrent radiochemotherapy. Experiments conducted both in vitro and in vivo confirmed that the knockdown of circRNF13 potentiated the radiosensitivity of CC cells. Further mechanistic studies revealed that METTL3/YTHDF2 promoted the degradation of circRNF13 and subsequently affected the stability of CXC motif chemokine ligand 1 (CXCL1), ultimately enhancing the radiosensitivity of CC cells. CONCLUSION This study identified circRNF13 as a novel m6A-modified circRNA and validated the METTL3/YTHDF2/circRNF13/CXCL1 axis as a potential target for CC radiotherapy.
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Affiliation(s)
- Junyu Shi
- Department of Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, PR China
| | - Xiaohui Rui
- Department of Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, PR China
| | - Chunxiao Han
- Department of Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, PR China
| | - Chaoping Wang
- Department of Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, PR China
| | - Lei Xu
- Department of Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, PR China
| | - Xiping Jiang
- Department of Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, PR China.
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Rao G, Peng X, Tian Y, Fu X, Zhang Y. Circular RNAs in hepatocellular carcinoma: biogenesis, function, and pathology. Front Genet 2023; 14:1106665. [PMID: 37485335 PMCID: PMC10361733 DOI: 10.3389/fgene.2023.1106665] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 06/16/2023] [Indexed: 07/25/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Both genetic and environmental factors through a multitude of underlying molecular mechanisms participate in the pathogenesis of HCC. Recently, numerous studies have shown that circular RNAs (circRNAs), an emerging class of non-coding RNAs characterized by the presence of covalent bonds linking 3' and 5' ends, play an important role in the initiation and progression of cancers, including HCC. In this review, we outline the current status of the field of circRNAs, with an emphasis on the functions and mechanisms of circRNAs in HCC and its microenvironment. We also summarize and discuss recent advances of circRNAs as biomarkers and therapeutic targets. These efforts are anticipated to throw new insights into future perspectives about circRNAs in basic, translational and clinical research, eventually advancing the diagnosis, prevention and treatment of HCC.
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Affiliation(s)
- Guocheng Rao
- Department of Endocrinology and Metabolism, Cancer Center West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Endocrinology and Metabolism, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Xi Peng
- Department of Endocrinology and Metabolism, Cancer Center West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Endocrinology and Metabolism, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Yan Tian
- Department of Endocrinology and Metabolism, Cancer Center West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xianghui Fu
- Department of Endocrinology and Metabolism, Cancer Center West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Endocrinology and Metabolism, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Yuwei Zhang
- Department of Endocrinology and Metabolism, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
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9
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Liu J, Kong L, Bian W, Lin X, Wei F, Chu J. circRNA_0001006 predicts prognosis and regulates cellular processes of triple-negative breast cancer via miR-424-5p. Cell Div 2023; 18:7. [PMID: 37194024 DOI: 10.1186/s13008-023-00089-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 04/23/2023] [Indexed: 05/18/2023] Open
Abstract
BACKGROUND circular RNAs (circRNAs) have been considered novel biomarker candidates for human cancers, such as triple-negative breast cancer (TNBC). circ_0001006 was identified as a differentially expressed circRNA in metastatic breast cancer, but its significance and function in TNBC were unclear. The significance of circ_0001006 in TNBC was assessed and exploring its potential molecular mechanism to provide a therapeutic target for TNBC. RESULTS circ_0001006 showed significant upregulation in TNBC and close association with patients' histological grade, Ki67 level, and TNM stage. Upregulated circ_0001006 could predict a worse prognosis and high risk of TNBC patients. In TNBC cells, silencing circ_0001006 suppressed cell proliferation, migration, and invasion. In mechanism, circ_0001006 could negatively regulate miR-424-5p, which mediated the inhibition of cellular processes by circ_0001006 knockdown. CONCLUSIONS Upregulated circ_0001006 in TNBC served as a poor prognosis predictor and tumor promoter via negatively regulating miR-424-5p.
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Affiliation(s)
- Jiaqi Liu
- Department of Breast and Thyroid Surgery, Zibo Central Hospital, 54 Gongqingtuan West Road, Zibo, 255020, China
| | - Linna Kong
- Department of Breast and Thyroid Surgery, Zibo Central Hospital, 54 Gongqingtuan West Road, Zibo, 255020, China
| | - Wenqing Bian
- Maternal and Child Health Hospital of Zibo, Zibo, 255095, China
| | - Xiaona Lin
- Department of Breast and Thyroid Surgery, Zibo Central Hospital, 54 Gongqingtuan West Road, Zibo, 255020, China
| | - Feifei Wei
- Weifang Maternal and Child Health Hospital, Weifang, 261000, China
| | - Jun Chu
- Department of Breast and Thyroid Surgery, Zibo Central Hospital, 54 Gongqingtuan West Road, Zibo, 255020, China.
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Song M, Liu J. Circ_0067717 promotes colorectal cancer cell growth, invasion and glutamine metabolism by serving as a miR-497-5p sponge to upregulate SLC7A5. Histol Histopathol 2023; 38:53-64. [PMID: 35818779 DOI: 10.14670/hh-18-494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Circular RNAs (circRNAs) have been shown to exert vital functions in colorectal cancer (CRC) development. However, the role of circ_0067717 in CRC progression remains to be elucidated. METHODS The expression of circ_0067717, microRNA (miR)-497-5p and solute carrier family 7 member 5 (SLC7A5) was analyzed by quantitative real-time PCR. Cell proliferation, apoptosis and invasion were determined by cell counting kit 8 assay, EdU assay, flow cytometry and transwell assay. Protein expression was examined using western blot analysis. Glutamine metabolism was assessed by measuring glutamine consumption, α-ketoglutarate production and glutamate production. The interaction between miR-497-5p and circ_0067717 or SLC7A5 was identified by dual-luciferase reporter assay. Xenograft tumor models were constructed to confirm the role of circ_0067717 in CRC tumorigenesis in vivo. RESULTS Our data revealed that circ_0067717 was upregulated in CRC tissues and cells, and its knockdown restrained CRC cell proliferation, invasion, glutamine metabolism, and promoted apoptosis. MiR-497-5p was lowly expressed in CRC and it could be sponged by circ_0067717. MiR-497-5p inhibitor eliminated the regulation of circ_0067717 knockdown on CRC cell function. SLC7A5 was targeted by miR-497-5p and was positively regulated by circ_0067717. MiR-497-5p overexpression suppressed CRC cell growth, invasion and glutamine metabolism, and SLC7A5 was able to revoke this effect. Animal experiments showed that interference of circ_0067717 reduced CRC tumor growth. CONCLUSION Our research pointed out that circ_0067717 facilitated CRC development depending on the regulation of the miR-497-5p/SLC7A5 axis, providing a novel insight into CRC treatment.
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Affiliation(s)
- Mo Song
- Department of Anorectal Surgery, Hengshui People's Hospital, Hengshui, China.
| | - Jipan Liu
- Department of Anorectal Surgery, Hengshui People's Hospital, Hengshui, China
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CircRNF13 Promotes the Malignant Progression of Pancreatic Cancer through Targeting miR-139-5p/IGF1R Axis. JOURNAL OF ONCOLOGY 2021; 2021:6945046. [PMID: 34899908 PMCID: PMC8664507 DOI: 10.1155/2021/6945046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 11/13/2021] [Indexed: 02/07/2023]
Abstract
Background Mounting evidence has shown circular RNAs (circRNAs) play an important role in the initiation and progression of pancreatic cancer (PC). Meanwhile, circRNAs may serve as the biomarkers for the diagnosis, treatment, and prognosis of PC. Therefore, it is urgent to elucidate the function and underlying mechanism of circRNAs in the development of PC. Methods The Cancer-Specific CircRNA Database (CSCD), Circular RNA Interactome database (circinteractome database), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to verify the expression level of circRNF13 in PC cell lines. Fluorescence in situ hybridization (FISH) and RNase protection assay were used to detect the localization and structure of circRNF13. Then, cell functional experiments were employed to estimate the proliferated, migrated, and invasive abilities in PC. Furthermore, bioinformatic tools, luciferase dual reporter assay, and RT-qPCR were used to investigate the interaction among circRNF13, miR-139-5p, and IGF1R. Eventually, the rescue functional experiments were employed to confirm that circRNF13 targeted the miR-139-5p/IGF1R axis to participate in the development of PC. Results CircRNF13 was overexpressed in PC cell lines compared with the normal pancreatic duct cell line. Additionally, inhibition of circRNF13 impaired the proliferation, migration, and invasion of PC cells. CircRNF13 could serve as the molecular sponge of miR-139-5p to inhibit its association with IGF1R that eventually accelerated the malignant progression of PC. Conclusion CircRNF13 serves as a competitive endogenous RNA of IGF1R to inhibit the function of miR-139-5p that eventually reinforces the malignant phenotype of PC.
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Pietropaolo V, Prezioso C, Moens U. Role of Virus-Induced Host Cell Epigenetic Changes in Cancer. Int J Mol Sci 2021; 22:ijms22158346. [PMID: 34361112 PMCID: PMC8346956 DOI: 10.3390/ijms22158346] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 07/30/2021] [Accepted: 08/02/2021] [Indexed: 12/12/2022] Open
Abstract
The tumor viruses human T-lymphotropic virus 1 (HTLV-1), hepatitis C virus (HCV), Merkel cell polyomavirus (MCPyV), high-risk human papillomaviruses (HR-HPVs), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV) and hepatitis B virus (HBV) account for approximately 15% of all human cancers. Although the oncoproteins of these tumor viruses display no sequence similarity to one another, they use the same mechanisms to convey cancer hallmarks on the infected cell. Perturbed gene expression is one of the underlying mechanisms to induce cancer hallmarks. Epigenetic processes, including DNA methylation, histone modification and chromatin remodeling, microRNA, long noncoding RNA, and circular RNA affect gene expression without introducing changes in the DNA sequence. Increasing evidence demonstrates that oncoviruses cause epigenetic modifications, which play a pivotal role in carcinogenesis. In this review, recent advances in the role of host cell epigenetic changes in virus-induced cancers are summarized.
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Affiliation(s)
- Valeria Pietropaolo
- Department of Public Health and Infectious Diseases, “Sapienza” University, 00185 Rome, Italy;
- Correspondence: (V.P.); (U.M.)
| | - Carla Prezioso
- Department of Public Health and Infectious Diseases, “Sapienza” University, 00185 Rome, Italy;
- IRCSS San Raffaele Roma, Microbiology of Chronic Neuro-Degenerative Pathologies, 00161 Rome, Italy
| | - Ugo Moens
- Molecular Inflammation Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, 9037 Tromsø, Norway
- Correspondence: (V.P.); (U.M.)
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