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FANG ZIYI, SHAO YONGFU, HU MENG, YAN JIANING, YE GUOLIANG. Biological roles and molecular mechanism of circular RNAs in epithelial-mesenchymal transition of gastrointestinal malignancies. Oncol Res 2025; 33:549-566. [PMID: 40109856 PMCID: PMC11915071 DOI: 10.32604/or.2024.051589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 06/13/2024] [Indexed: 03/22/2025] Open
Abstract
Circular RNAs (circRNAs) are formed by splicing of precursor RNAs and covalently linked at the 5' and 3' ends. Dysregulated circRNAs are closely related to the epithelial-mesenchymal transition (EMT) of gastrointestinal malignancies. CircRNAs, including circRNA_0008717, circGOT1, circ-DOCK5, circVPS33B, circPVT1, circMET, circ-OXCT1, circ_67835, circRTN4, circ_0087502, circFNDC38, circ_PTEN1, circPGPEP1, and circ-E-Cad are involved in the EMT process of gastrointestinal malignancies through a variety of mechanisms, such as regulating EMT-inducing transcription factors, signaling pathways, and tumor microenvironments. Gastrointestinal (GI) malignancies are common malignant tumors worldwide, and the heterogeneity and easy metastasis of gastrointestinal malignancies limit the effectiveness of medical treatments. Therefore, investigating the molecular mechanisms involved in the pathogenesis of gastrointestinal malignancies is essential for clinical treatment. This article summarizes the biological roles and molecular mechanism of circRNAs in EMT of gastrointestinal malignancies, providing a theoretical basis for applying EMT-related circRNAs in targeted therapy.
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Affiliation(s)
- ZIYI FANG
- School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, 315211, China
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315020, China
| | - YONGFU SHAO
- School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, 315211, China
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315020, China
| | - MENG HU
- School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, 315211, China
| | - JIANING YAN
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315020, China
| | - GUOLIANG YE
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315020, China
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Shakerian N, Darzi-Eslam E, Afsharnoori F, Bana N, Noorabad Ghahroodi F, Tarin M, Mard-Soltani M, Khalesi B, Hashemi ZS, Khalili S. Therapeutic and diagnostic applications of exosomes in colorectal cancer. Med Oncol 2024; 41:203. [PMID: 39031221 DOI: 10.1007/s12032-024-02440-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/26/2024] [Indexed: 07/22/2024]
Abstract
Exosomes play a key role in colorectal cancer (CRC) related processes. This review explores the various functions of exosomes in CRC and their potential as diagnostic markers, therapeutic targets, and drug delivery vehicles. Exosomal long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) significantly influence CRC progression. Specific exosomal lncRNAs are linked to drug resistance and tumor growth, respectively, highlighting their therapeutic potential. Similarly, miRNAs like miR-21, miR-10b, and miR-92a-3p, carried by exosomes, contribute to chemotherapy resistance by altering signaling pathways and gene expression in CRC cells. The review also discusses exosomes' utility in CRC diagnosis. Exosomes from cancer cells have distinct molecular signatures compared to healthy cells, making them reliable biomarkers. Specific exosomal lncRNAs (e.g., CRNDE-h) and miRNAs (e.g., miR-17-92a) have shown effectiveness in early CRC detection and monitoring of treatment responses. Furthermore, exosomes show promise as vehicles for targeted drug delivery. The potential of mesenchymal stem cell (MSC)-derived exosomes in CRC treatment is also noted, with their role varying from promoting to inhibiting tumor progression. The application of multi-omics approaches to exosome research is highlighted, emphasizing the potential for discovering novel CRC biomarkers through comprehensive genomic, transcriptomic, proteomic, and metabolomic analyses. The review also explores the emerging field of exosome-based vaccines, which utilize exosomes' natural properties to elicit strong immune responses. In conclusion, exosomes represent a promising frontier in CRC research, offering new avenues for diagnosis, treatment, and prevention. Their unique properties and versatile functions underscore the need for continued investigation into their clinical applications and underlying mechanisms.
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Affiliation(s)
- Neda Shakerian
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Elham Darzi-Eslam
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Fatemeh Afsharnoori
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Nikoo Bana
- Kish International Campus, University of Teheran, Tehran, Iran
| | - Faezeh Noorabad Ghahroodi
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mojtaba Tarin
- Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Maysam Mard-Soltani
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Bahman Khalesi
- Department of Research and Production of Poultry Viral Vaccine, Education and Extension Organization, Razi Vaccine and Serum Research Institute, Agricultural Research, Karaj, 3197619751, Iran
| | - Zahra Sadat Hashemi
- ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
| | - Saeed Khalili
- Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran.
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Bakinowska E, Kiełbowski K, Skórka P, Dach A, Olejnik-Wojciechowska J, Szwedkowicz A, Pawlik A. Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer-A Narrative Review. Int J Mol Sci 2024; 25:5144. [PMID: 38791187 PMCID: PMC11121563 DOI: 10.3390/ijms25105144] [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: 04/08/2024] [Revised: 05/03/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Non-coding RNAs (ncRNAs) represent a broad family of molecules that regulate gene expression, including microRNAs, long non-coding RNAs and circular RNAs, amongst others. Dysregulated expression of ncRNAs alters gene expression, which is implicated in the pathogenesis of several malignancies and inflammatory diseases. Gastric cancer is the fifth most frequently diagnosed cancer and the fourth most common cause of cancer-related death. Studies have found that altered expression of ncRNAs may contribute to tumourigenesis through regulating proliferation, apoptosis, drug resistance and metastasis. This review describes the potential use of ncRNAs as diagnostic and prognostic biomarkers. Moreover, we discuss the involvement of ncRNAs in the pathogenesis of gastric cancer, including their interactions with the members of major signalling pathways.
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Affiliation(s)
| | | | | | | | | | | | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (E.B.); (K.K.); (P.S.); (A.D.); (J.O.-W.); (A.S.)
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Feng XY, Zhu SX, Pu KJ, Huang HJ, Chen YQ, Wang WT. New insight into circRNAs: characterization, strategies, and biomedical applications. Exp Hematol Oncol 2023; 12:91. [PMID: 37828589 PMCID: PMC10568798 DOI: 10.1186/s40164-023-00451-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 09/23/2023] [Indexed: 10/14/2023] Open
Abstract
Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns, epigenetic regulation, translation potential, localization and metabolism. Increasing evidence has revealed that circRNAs participate in diverse cellular processes, and their dysregulation is involved in the pathogenesis of various diseases, particularly cancer. In this review, we systematically discuss the characterization of circRNAs, databases, challenges for circRNA discovery, new insight into strategies used in circRNA studies and biomedical applications. Although recent studies have advanced the understanding of circRNAs, advanced knowledge and approaches for circRNA annotation, functional characterization and biomedical applications are continuously needed to provide new insights into circRNAs. The emergence of circRNA-based protein translation strategy will be a promising direction in the field of biomedicine.
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Affiliation(s)
- Xin-Yi Feng
- MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China
| | - Shun-Xin Zhu
- MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China
| | - Ke-Jia Pu
- MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China
| | - Heng-Jing Huang
- MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China
| | - Yue-Qin Chen
- MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China.
| | - Wen-Tao Wang
- MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China.
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Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights. Int J Biol Macromol 2022; 220:973-984. [PMID: 35977596 DOI: 10.1016/j.ijbiomac.2022.08.085] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/19/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.
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Li Z, Xie Y, Xiao B, Guo J. The tumor suppressor function of hsa_circ_0006282 in gastric cancer through PTEN/AKT pathway. Int J Clin Oncol 2022; 27:1562-1569. [PMID: 35794253 DOI: 10.1007/s10147-022-02210-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 06/20/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer. METHODS The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis. RESULTS Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p. CONCLUSION By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer.
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Affiliation(s)
- Zhe Li
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China
| | - Yi Xie
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China
| | - Junming Guo
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China.
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
- Institute of Digestive Diseases of Ningbo University, Ningbo, 315020, China.
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Chen C, Xia C, Tang H, Jiang Y, Wang S, Zhang X, Huang T, Yuan X, Wang J, Peng L. Circular RNAs Involve in Immunity of Digestive Cancers From Bench to Bedside: A Review. Front Immunol 2022; 13:833058. [PMID: 35464462 PMCID: PMC9020258 DOI: 10.3389/fimmu.2022.833058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
The immune system plays a complex role in tumor formation and development. On the one hand, immune surveillance can inhibit the growth of tumors; on the other hand, immune evasion of tumors can create conditions conducive for tumor development and growth. CircRNAs are endogenous non-coding RNAs with a covalently closed loop structure that are abundantly expressed in eukaryotic organisms. They are characterized by stable structure, rich diversity, and high evolutionary conservation. In particular, circRNAs play a vital role in the occurrence, development, and treatment of tumors through their unique functions. Recently, the incidence and mortality of digestive cancers, especially those of gastric cancer, colorectal cancer, and liver cancer, have remained high. However, the functions of circRNAs in digestive cancers immunity are less known. The relationship between circRNAs and digestive tumor immunity is systematically discussed in our paper for the first time. CircRNA can influence the immune microenvironment of gastrointestinal tumors to promote their occurrence and development by acting as a miRNA molecular sponge, interacting with proteins, and regulating selective splicing. The circRNA vaccine even provides a new idea for tumor immunotherapy. Future studies should be focused on the location, transportation, and degradation mechanisms of circRNA in living cells and the relationship between circRNA and tumor immunity. This paper provides a new idea for the diagnosis and treatment of gastrointestinal tumors.
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Affiliation(s)
- Chunyue Chen
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Congcong Xia
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Hao Tang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Yirun Jiang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Shan Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
- Department of Pathology, School of Basic Medicine, Central South University, Changsha, China
| | - Xin Zhang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
- Department of Pathology, School of Basic Medicine, Central South University, Changsha, China
| | - Tao Huang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
- Department of Pathology, School of Basic Medicine, Central South University, Changsha, China
| | - Xiaoqing Yuan
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Junpu Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
- Department of Pathology, School of Basic Medicine, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Li Peng, ; Junpu Wang,
| | - Li Peng
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Li Peng, ; Junpu Wang,
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Shao Y, Qi C, Yan J, Lu R, Ye G, Guo J. Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application. J Clin Lab Anal 2022; 36:e24369. [PMID: 35334500 PMCID: PMC9102612 DOI: 10.1002/jcla.24369] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/01/2022] [Accepted: 03/13/2022] [Indexed: 12/13/2022] Open
Abstract
Background Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. Methods Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan–Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. Results Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease‐free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease‐free survival time. The nomograms showed good accuracy of predicting survival time. Conclusion Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced‐stage patients.
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Affiliation(s)
- Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Changlei Qi
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Jianing Yan
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Rongdan Lu
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
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CircRNAs as Potential Blood Biomarkers and Key Elements in Regulatory Networks in Gastric Cancer. Int J Mol Sci 2022; 23:ijms23020650. [PMID: 35054834 PMCID: PMC8776217 DOI: 10.3390/ijms23020650] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/02/2022] [Accepted: 01/04/2022] [Indexed: 12/21/2022] Open
Abstract
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.
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Hong C, Lishan W, Peng X, Zhengqing L, Yang Y, Fangfang H, Zeqian Y, Zhangjun C, Jiahua Z. Hsa_circ_0074298 promotes pancreatic cancer progression and resistance to gemcitabine by sponging miR-519 to target SMOC. J Cancer 2022; 13:34-50. [PMID: 34976169 PMCID: PMC8692684 DOI: 10.7150/jca.62927] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 11/05/2021] [Indexed: 01/06/2023] Open
Abstract
Objective: To investigate the expression of hsa_circ_0074298 (circular RNA) and the molecular mechanism that promotes tumor growth and enhances the chemoresistance of pancreatic cancer. Methods: Real-time reverse transcription-PCR was used to detect hsa_circ_0074298 expression in pancreatic cancer. The intracellular localization of hsa_circ_0074298 was determined by RNA in situ hybridization. The CCK8 method, colony formation assay, Transwell assay, and flow cytometry were used to evaluate the effects of hsa_circ_0074298 on the proliferation, migration, invasion, cell cycle, apoptosis of pancreatic cancer cells. Bioinformatics analysis and dual luciferase assays were employed to detect the association of hsa_circ_0074298 and miR-519d and the binding of miR-519d to the target gene SMOC2. A subcutaneous xenograft model was established to observe the effect of hsa_circ_0074298 in vivo. Results: The hsa_circ_0074298 was mainly localized in the cytoplasm. Hsa_circ_0074298 was highly expressed in pancreatic cancer tissues and cell lines. The expression of hsa_circ_0074298 was significantly correlated with pancreatic cancer tumor size, lymph node metastasis, and pathological grade. hsa_circ_0074298 could sponge miR-519, and miR-519d bound to SMOC2. Downregulation of hsa_circ_0074298 expression significantly inhibited cell proliferation, migration, invasion, colony forming ability and promoted cell cycle arrest, apoptosis and chemo-resistance of pancreatic cancer in vitro and vivo. However, the effects could be reversed by a miR-519d inhibitor or SMOC2 overexpression. Conclusion: By sponging miR-519 and targeting SMOC2, hsa_circ_0074298 promotes the growth and metastasis of pancreatic cancer and increases the resistance of pancreatic cancer cells to gemcitabine.
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Affiliation(s)
- Chen Hong
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Wang Lishan
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Xie Peng
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Lei Zhengqing
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Yang Yang
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Hu Fangfang
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Yu Zeqian
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Cheng Zhangjun
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Zhou Jiahua
- Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China
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11
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Shi P, Song H, Ding X. Reduced expression of circRNA hsa_circ_001888 in gastric cancer and its clinical significance. J Clin Lab Anal 2021; 35:e23953. [PMID: 34398999 PMCID: PMC8418507 DOI: 10.1002/jcla.23953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/31/2021] [Accepted: 08/02/2021] [Indexed: 12/14/2022] Open
Abstract
Background Circular RNAs (circRNAs) are a novel family of endogenous RNAs. Recent studies have demonstrated that circRNAs are potential novel biomarkers for diagnosing cancers. However, little is known about the role of circRNAs in gastric cancer (GC). This study aimed to identify the relationship between GC and a new circRNA named hsa_circ_001888. Methods Hsa_circ_001888 expression levels were measured by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in GC cell lines, tissues, and plasma samples. Then, the associations between the expression level of hsa_circ_001888 and the clinicopathological features of patients with GC were further investigated. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value of hsa_circ_001888. Results In this study, hsa_circ_001888 was first found to be significantly downregulated in GC cell lines (AGS and MKN‐45), tissues, and plasma samples compared to control samples. Clinicopathological features showed that the expression of hsa_circ_001888 in GC tissues was associated with differentiation and in GC plasma linked with serum CEA and CA19‐9 levels. The areas under the ROC curves of hsa_circ_001888 in tissues and plasma were 0.654 and 0.66, respectively. Conclusions Hsa_circ_001888 may serve as a potential biomarker in the diagnosis of GC and may be involved in GC development.
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Affiliation(s)
- Peina Shi
- The Gastroenterology Department of Ningbo First Hospital, Ningbo, China.,The Gastroenterology Department of Ningbo Yinzhou No. 2 Hospital, Ningbo, China
| | - Haojun Song
- The Gastroenterology Department of Ningbo First Hospital, Ningbo, China
| | - Xiaoyun Ding
- The Gastroenterology Department of Ningbo First Hospital, Ningbo, China
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12
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Advani D, Sharma S, Kumari S, Ambasta RK, Kumar P. Precision Oncology, Signaling and Anticancer Agents in Cancer Therapeutics. Anticancer Agents Med Chem 2021; 22:433-468. [PMID: 33687887 DOI: 10.2174/1871520621666210308101029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/05/2021] [Accepted: 01/12/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The global alliance for genomics and healthcare facilities provides innovational solutions to expedite research and clinical practices for complex and incurable health conditions. Precision oncology is an emerging field explicitly tailored to facilitate cancer diagnosis, prevention and treatment based on patients' genetic profile. Advancements in "omics" techniques, next-generation sequencing, artificial intelligence and clinical trial designs provide a platform for assessing the efficacy and safety of combination therapies and diagnostic procedures. METHOD Data were collected from Pubmed and Google scholar using keywords: "Precision medicine", "precision medicine and cancer", "anticancer agents in precision medicine" and reviewed comprehensively. RESULTS Personalized therapeutics including immunotherapy, cancer vaccines, serve as a groundbreaking solution for cancer treatment. Herein, we take a measurable view of precision therapies and novel diagnostic approaches targeting cancer treatment. The contemporary applications of precision medicine have also been described along with various hurdles identified in the successful establishment of precision therapeutics. CONCLUSION This review highlights the key breakthroughs related to immunotherapies, targeted anticancer agents, and target interventions related to cancer signaling mechanisms. The success story of this field in context to drug resistance, safety, patient survival and in improving quality of life is yet to be elucidated. We conclude that, in the near future, the field of individualized treatments may truly revolutionize the nature of cancer patient care.
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Affiliation(s)
- Dia Advani
- Molecular Neuroscience and Functional Genomics Laboratory Shahbad Daulatpur, Bawana Road, Delhi 110042. India
| | - Sudhanshu Sharma
- Molecular Neuroscience and Functional Genomics Laboratory Shahbad Daulatpur, Bawana Road, Delhi 110042. India
| | - Smita Kumari
- Molecular Neuroscience and Functional Genomics Laboratory Shahbad Daulatpur, Bawana Road, Delhi 110042. India
| | - Rashmi K Ambasta
- Molecular Neuroscience and Functional Genomics Laboratory Shahbad Daulatpur, Bawana Road, Delhi 110042. India
| | - Pravir Kumar
- Molecular Neuroscience and Functional Genomics Laboratory Shahbad Daulatpur, Bawana Road, Delhi 110042. India
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13
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Liu C, Chen M, Shi Y. Downregulation of hsa_circ_0006220 and its correlation with clinicopathological factors in human breast cancer. Gland Surg 2021; 10:816-825. [PMID: 33708563 DOI: 10.21037/gs-21-42] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background Circular ribonucleic acids (circRNAs) are highly stable and conserved forms of RNAs present in all eukaryotes. They can modulate the expression of genes by sponging specific micro RNAs (miRNAs), thereby affecting various disease processes. However, their expression pattern in human breast cancer has not been elucidated. Methods In this study, differentially expressed circRNAs in breast cancer tissues and paired noncancerous tissues were analyzed using an Arraystar Human circRNA Microarray, and hsa_circ_0006220 was selected for its 27-fold downregulation in breast cancer tissues. Its expression was also verified in 50 breast cancer and paired noncancerous tissues using real-time polymerase chain reaction (RT-PCR). An analysis of the expression of hsa_circ_0006220 and the clinicopathological factors in breast cancer was conducted. A receiver operating characteristic (ROC) curve of hsa_circ_0006220 was constructed. The interaction between hsa_circ_0006220 and five possible target miRNAs was predicted, and their expression were verified when overexpressing hsa_circ_0006220 by RT-PCR. Results Hsa_circ_0006220 was found to be significantly downregulated in breast cancer tissues compared to the paired noncancerous tissues by microarray and RT-PCR. The expression of hsa_circ_0006220 was significantly inversely correlated with histological type (P=0.0028) and lymph node metastasis (P=0.0341). The area under the ROC curve (AUC) was 0.706. Five miRNAs that might be sponged by hsa_circ_0006220 were predicted. MiR-197-5p was significantly downregulated after overexpression of hsa_circ_0006220. Conclusions Our results indicated that hsa_circ_0006220 may play a role in human breast cancer and might be a potential tumor marker for breast cancer screening.
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Affiliation(s)
- Chong Liu
- Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Mingshi Chen
- Traditional Chinese Medicine Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yue Shi
- Department of Geriatric Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
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14
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Tang X, Ren H, Guo M, Qian J, Yang Y, Gu C. Review on circular RNAs and new insights into their roles in cancer. Comput Struct Biotechnol J 2021; 19:910-928. [PMID: 33598105 PMCID: PMC7851342 DOI: 10.1016/j.csbj.2021.01.018] [Citation(s) in RCA: 237] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/13/2021] [Accepted: 01/14/2021] [Indexed: 12/13/2022] Open
Abstract
Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5'end cap and 3'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.
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Key Words
- AML, acute myloid leukemia
- BSJ, back-splice junction
- Biomarker
- CLL, chronic lymphocytic leukemia
- CML, chronic myeloid leukemia
- CRC, colorectal cancer
- Cancer
- Circular RNAs
- EIciRNAs, exon–intron RNAs
- EMT, epithelial-mesenchymal transition
- Functions
- GC, gastric cancer
- HCC, hepatocellular carcinoma
- ISH, in situ hybridization
- LUAD, lung adenocarcinoma
- MER, miRNA response elements
- MM, multiple myeloma
- NSCLC, non-small cell lung cancer
- PCR, polymerase chain reaction
- PDAC, pancreatic ductal adenocarcinoma
- RBP, RNA-binding protein
- RNA, ribonucleic acid
- RNase, ribonuclease
- RT-PCR, reverse transcription-PCR
- TNM, tumor node metastases
- UTR, untranslated regions
- ccRCC, clear cell renal cell carcinoma
- ceRNAs, endogenous RNAs
- ciRNAs, circular intronic RNAs
- ciRS-7, circular RNA sponge for miR-7
- circRNAs, circular RNAs
- ecircRNAs, exonic circular RNAs
- lncRNAs, long ncRNA
- miRNAs, microRNAs
- ncRNAs, noncoding RNAs
- qPCR, quantitative PCR
- rRNA, ribosomal RNA
- siRNAs, small interfering RNAs
- snRNA, small nuclear RNA
- tricRNAs, tRNA intronic circRNAs
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Affiliation(s)
- Xiaozhu Tang
- The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Hongyan Ren
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Mengjie Guo
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jinjun Qian
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Ye Yang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Chunyan Gu
- The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
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15
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Cheng D, Wang J, Dong Z, Li X. Cancer-related circular RNA: diverse biological functions. Cancer Cell Int 2021; 21:11. [PMID: 33407501 PMCID: PMC7789196 DOI: 10.1186/s12935-020-01703-z] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 12/04/2020] [Indexed: 02/06/2023] Open
Abstract
Noncoding RNAs, including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in regulating biological functions. In recent decades, miRNAs and lncRNAs have both inspired a wave of research, but the study of circRNA functions is still in its infancy. Studies have found that circRNAs actively participate in the occurrence and development of various diseases, which emphasizes the importance of circRNAs. Here, we review the features and classification of circRNAs and summarize their functions. Then, we briefly describe how to analyze circRNAs by bioinformatics procedures. In addition, the relationship between circRNAs and cancers is discussed with an emphasis on proving whether circRNAs can be potential biomarkers for the prognosis and diagnosis of cancer.
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Affiliation(s)
- Dan Cheng
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China
| | - Jing Wang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China
| | - Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China
| | - Xiang Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. .,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China.
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16
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Khanipouyani F, Akrami H, Fattahi MR. Circular RNAs as important players in human gastric cancer. Clin Transl Oncol 2021; 23:10-21. [PMID: 32583185 DOI: 10.1007/s12094-020-02419-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 06/04/2020] [Indexed: 01/17/2023]
Abstract
As one of the most prevalent gastrointestinal diseases, gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. Since GC has no clinical manifestations in the early stage of the disease, most patients are detected in the later phases of disease and have an unfortunately lower chance of recovery. Circular RNAs (circRNAs), a novel category of non-coding RNAs (ncRNAs), are mainly engaged in the regulation of gene expression at the transcriptional and post-transcriptional levels. Numerous evidences have revealed that circRNAs play key roles in GC as they are involved in cell proliferation, growth, and apoptosis via modulating the expression of some target genes, miRNAs, and proteins. Many studies have addressed the impact of circRNA dysregulation on GC initiation, progression, and invasion via binding to miRNAs or RNA binding proteins. Moreover, changes in circRNA expression are associated with pathological and clinical features of GC highlighting their potentials as diagnostic or prognostic biomarkers in GC. In the current study, the recent findings on the significance of circRNAs in the development and progression of GC are reviewed. We focus on the implications of circRNAs as potential diagnostic or prognostic biomarkers in this malignancy.
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Affiliation(s)
- F Khanipouyani
- Department of Biology, Faculty of Science, Razi University, kermanshah, Iran
| | - H Akrami
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - M R Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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17
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Wang M, Gong Z, Zhao X, Yu W, Huang F, Dong H. Circular RNAs emerge as important regulators with great potential for clinical application in gastric cancer. Biomark Med 2021; 15:69-82. [PMID: 33185463 DOI: 10.2217/bmm-2020-0591] [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: 09/10/2020] [Accepted: 10/28/2020] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer (GC) is a common digestive malignancy with a high-ranking morbidity and mortality. Therefore, it is urgent to identify novel indicators and develop new strategies for clinical diagnosis and treatment of GC. As a type of noncoding RNA, circular RNAs (circRNAs) have received increased attention in GC during recent years. To more comprehensively understand current research progress on circRNAs in GC, in this review, we introduce basic knowledge of circRNAs, summarize abnormally expressed circRNAs and discuss their functions and regulatory molecular mechanisms in GC. Then, we review potential applications of circRNAs for GC diagnosis, prognosis and treatment. Finally, we conclude by highlighting major advancements of circRNAs in GC research, and we discuss existing challenges and possible future research directions of GC-associated circRNAs.
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Affiliation(s)
- Mei Wang
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Zheng Gong
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Xinxin Zhao
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Wanjun Yu
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Feng Huang
- Department of Clinical Laboratory, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Suzhou, Jiangsu Province 215300, China
| | - Haibo Dong
- Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Gulou District, Nanjing, Jiangsu Province 210008, China
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18
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Rajappa A, Banerjee S, Sharma V, Khandelia P. Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics. Front Mol Biosci 2020; 7:577938. [PMID: 33195421 PMCID: PMC7655967 DOI: 10.3389/fmolb.2020.577938] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/26/2020] [Indexed: 12/17/2022] Open
Abstract
Circular RNAs (circRNAs) are rapidly coming to the fore as major regulators of gene expression and cellular functions. They elicit their influence via a plethora of diverse molecular mechanisms. It is not surprising that aberrant circRNA expression is common in cancers and they have been implicated in multiple aspects of cancer pathophysiology such as apoptosis, invasion, migration, and proliferation. We summarize the emerging role of circRNAs as biomarkers and therapeutic targets in cancer.
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Affiliation(s)
| | | | - Vivek Sharma
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad, India
| | - Piyush Khandelia
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad, India
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19
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Tan XY, Zhao ZL, Lin F, Luo M. Role of circular RNAs in digestive system tumors. Shijie Huaren Xiaohua Zazhi 2020; 28:951-958. [DOI: 10.11569/wcjd.v28.i19.951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Circular RNAs (circRNAs), a class of endogenous closed-loop noncoding RNAs, are expressed widely in all kinds of eukaryotic cells and have the characteristics of stable structure, high conservation, cell specificity, and tissue specificity. Several studies have revealed that circRNAs are closely related to the occurrence and development of cardiovascular system diseases, nervous system diseases, tumors, and other diseases. Recently, more and more studies have indicated that circRNAs have good clinical efficacy in the diagnosis and treatment of digestive system tumors, and they are expected to become biomarkers for early diagnosis and new therapeutic targets for the development of novel anticancer drugs. Therefore, it has become a hot topic of the current and future development direction in clinical research. circRNAs play a dual role in the pathological evolution of digestive system tumors, wherein they acting as miRNA sponges could play significant roles in carcinogenesis and anticarcinogenesis. This paper reviews the biological characteristics of circRNAs, summarizes the research progress of circRNAs in digestive system tumors, and discusses the potential use of circRNAs as targets for prevention, diagnosis, and treatment of digestive system tumors in the future.
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Affiliation(s)
- Xiao-Yong Tan
- Pharmaceutical Department, Xuanhan County People's Hospital, Dazhou 636150, Sichuan Province, China
| | - Zai-Lin Zhao
- Pharmaceutical Department, Xuanhan County People's Hospital, Dazhou 636150, Sichuan Province, China
| | - Fang Lin
- Drug Discovery Research Center, Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Mao Luo
- Drug Discovery Research Center, Southwest Medical University, Luzhou 646000, Sichuan Province, China
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20
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MetaDE-Based Analysis of circRNA Expression Profiles Involved in Gastric Cancer. Dig Dis Sci 2020; 65:2884-2895. [PMID: 31894486 DOI: 10.1007/s10620-019-06014-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 12/12/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Circular RNAs (circRNAs) could play carcinogenic roles in gastric cancer (GC) and have potential to be biomarkers for GC early diagnosis, which needs to be further excavated and supported by more evidence. AIMS The study aims to identify more authentic circRNA expression profiles that could function as potential biomarkers in GC. METHODS circRNA expression data in three microarrays were downloaded from Gene Expression Omnibus datasets. A systematic meta-analysis based on an integrated dataset pre-processed from the three microarrays was conducted to identify a panel of differentially expressed circRNAs (DEcircs) by using the metaDE package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment were used to note the corresponding functions of DEcircs. Quantitative real-time polymerase chain reaction was applied to verify the DEcircs expression in cancer tissues and adjacent paracancerous tissues. A GC risk-related circRNAs-miRNAs-mRNAs network was further constructed and analyzed. RESULTS MetaDE analysis suggested 64 DEcircs between cancer tissues and adjacent normal tissues. GO and KEGG analysis showed that the parental genes of these DEcircs were mainly associated with histone methylation, Wnt signalosome and histone methylation activity. Hsa_circ_0005927 and hsa_circ_0067934 were verified in GC tissues, and a GC risk-related network was constructed. CONCLUSION MetaDE-based circRNA expression profiles revealed a series of potential biomarkers involved in GC. Two circRNAs, hsa_circ_0005927 and hsa_circ_0067934, could be more authentic biomarkers for GC screening. The GC risk-related network of hsa_circ_0005927/hsa_circ_0067934 and their downstream targets will provide new genetic insights for GC research.
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21
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Fan YX, Shi HY, Hu YL, Jin XL. Circ_0000144 facilitates the progression of thyroid cancer via the miR-217/AKT3 pathway. J Gene Med 2020; 22:e3269. [PMID: 32890417 DOI: 10.1002/jgm.3269] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 08/26/2020] [Accepted: 08/29/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Thyroid carcinoma (TC) is the most common malignancy of the endocrine system. Circular RNA (circRNA) is vital in the regulation of tumor progression. Circ_0000144 serves as a novel oncogenic circRNA, and miR-217 is reported to inhibit the malignant phenotypes of cancer cells by targeting AKT3 in TC. The present study aimed to explore the regulatory mechanism of circ_0000144 and miR-217 in the progression of TC. METHODS Circ_0000144 expression in 32 pairs of TC tissues and different TC cell lines (including BCPAP, K1, H7H83, and TPC-1) was detected by employing a quantitative real-time polymerase chain reaction (qRT-PCR). Circ_0000144 small interfering RNA was used to establish loss-of-function models. Cell counting kit-8 (CCK-8), BrdU (5-bromo-2'-deoxyuridine) and transwell assays were utilized to verify the effects of circ_0000144 on TC cell proliferation, migration and invasion, respectively. Bioinformatics, western blotting, a luciferase reporter experiment and qRT-PCR were employed to confirm the relationships among circ_0000144, miR-217 and AKT3. RESULTS Circ_0000144 expression was remarkably elevated in TC tissues (p < 0.001) and TC cell lines. The elevation of circ_0000144 expression was markedly linked to tumor size (p = 0.015), TNM stage (p = 0.025) and lymph node metastasis (p = 0.017) of the patients. Functional studies showed that knocking down circ_0000144 repressed the malignancy of TC cells. Furthermore, miR-217 was identified as a downstream target of circ_0000144; inhibition of miR-217 could reverse the effects induced by circ_0000144 knockdown. Moreover, circ_0000144 could regulate AKT3 expression by suppressing miR-217 expression. CONCLUSIONS Circ_0000144 exerts a cancer-promoting effect on TC cells via the miR-217/AKT3 pathway.
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Affiliation(s)
- Yi-Xiang Fan
- Department of Nuclear Medicine, The Fifth Affiliated Hospital of Southern Medical University, Conghua District, Guangzhou, China
| | - Huan-Yang Shi
- The Clinical Specialty 5-Year Undergraduate Course, The First Clinical Medical College of Southern Medical University, Guangzhou, China
| | - Yu-Lin Hu
- Department of Nuclear Medicine, The Fifth Affiliated Hospital of Southern Medical University, Conghua District, Guangzhou, China
| | - Xiao-Li Jin
- Department of Nuclear Medicine, The Fifth Affiliated Hospital of Southern Medical University, Conghua District, Guangzhou, China
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22
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Abstract
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.
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23
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Circular RNAs in Gastric Cancer: Potential Biomarkers and Therapeutic Targets. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2790679. [PMID: 32685459 PMCID: PMC7345955 DOI: 10.1155/2020/2790679] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 05/29/2020] [Accepted: 06/01/2020] [Indexed: 12/15/2022]
Abstract
Circular RNAs (circRNAs), as a recently established group of endogenous noncoding RNAs, have been involved in the occurrence and development of different malignancies. Gastric cancer (GC) remains a globally significant contributor to death in cancer patients due to insufficient early diagnosis, limited treatment measures, and poor prognosis. An increasing number of studies have found that many circRNAs are dysregulated in GC and are closely associated with its tumorigenesis and metastasis. Thus, circRNAs have the potential to serve as diagnostic and prognostic biomarkers and even therapeutic targets. This review comprehensively summarizes the most recent findings on how circRNAs influence GC progression and their clinical value. In addition, we present several methological deficiencies in the studies and provide some promising ideas for future research.
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24
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Wang HY, Wang YP, Zeng X, Zheng Y, Guo QH, Ji R, Zhou YN. Circular RNA is a popular molecule in tumors of the digestive system (Review). Int J Oncol 2020; 57:21-42. [PMID: 32377736 PMCID: PMC7252451 DOI: 10.3892/ijo.2020.5054] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/06/2020] [Indexed: 02/06/2023] Open
Abstract
Most tumors of the digestive system, including esophageal, gastric, liver and colorectal cancer, are malignant tumors that are associated with rates of high morbidity and mortality. The lack of effective methods for early diagnosis is an important cause of poor prognosis for these malignancies. Circular RNAs (circRNAs) belong to a family of endogenous, covalently closed non‑coding RNAs that are characterized as having no 5' cap structures or 3' poly‑A tails. Shortly following discovery, circRNAs were considered to be a product of mis‑splicing and have no significant biological function. However, in recent years, accumulating evidence is demonstrating that they serve key roles in tumorigenesis and have the potential to serve as diagnostic markers. The present article summarizes the biogenesis and function of circRNAs and reviews their role in seven common types of tumor of the digestive system whilst exploring their potential as tumor markers and the significant roles they can serve in the digestive system, in addition to providing a referencing point for future studies of digestive system malignancies.
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Affiliation(s)
- Hao-Ying Wang
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yu-Ping Wang
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Xi Zeng
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Ya Zheng
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Qing-Hong Guo
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Rui Ji
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yong-Ning Zhou
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
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Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W. CircRNA: a rising star in gastric cancer. Cell Mol Life Sci 2020; 77:1661-1680. [PMID: 31659415 PMCID: PMC11104848 DOI: 10.1007/s00018-019-03345-5] [Citation(s) in RCA: 274] [Impact Index Per Article: 54.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 10/08/2019] [Accepted: 10/14/2019] [Indexed: 01/17/2023]
Abstract
In recent years, a large number of circRNAs have been identified in mammalian cells with high-throughput sequencing technologies and bioinformatics. The aberrant expression of circRNAs has been reported in many human diseases including gastric cancer (GC). The number of GC-related circRNAs with validated biological functions and mechanisms of action is growing. CircRNAs are critically involved in GC cell proliferation, apoptosis, migration, and invasion. CircRNAs have been shown to function as regulators of parental gene transcription and alternative splicing and miRNA sponges. Moreover, circRNAs have been suggested to interact with proteins to regulate their expression level and activities. Several circRNAs have been identified to encode functional proteins. Due to their great abundance, high stability, tissue- and developmental-stage-specific expression patterns, and wide distribution in various body fluids and exosomes, circRNAs exhibit a great potential to be utilized as biomarkers for GC. Herein, we briefly summarize their biogenesis, properties and biological functions and discuss about the current research progress of circRNAs in GC with a focus on the potential application for GC diagnosis and therapy.
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Affiliation(s)
- Rong Li
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Jiajia Jiang
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China
| | - Hui Shi
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Hui Qian
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Xu Zhang
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China.
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
| | - Wenrong Xu
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China.
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
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26
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Xu Y, Yu J, Huang Z, Fu B, Tao Y, Qi X, Mou Y, Hu Y, Wang Y, Cao Y, Jiang D, Xie J, Xu Y, Zhao J, Xiong W. Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2020; 39:57. [PMID: 32248836 PMCID: PMC7132982 DOI: 10.1186/s13046-020-01556-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 03/08/2020] [Indexed: 12/31/2022]
Abstract
Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. Methods In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. Results We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Conclusions Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.
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Affiliation(s)
- Yuzhu Xu
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China.,Department of Respiratory, Zhuzhou Central Hospital, Zhuzhou, China
| | - Jun Yu
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhenli Huang
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Bohua Fu
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yu Tao
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Xuefei Qi
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yong Mou
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yinan Hu
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yi Wang
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yong Cao
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Dingsheng Jiang
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jungang Xie
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yongjian Xu
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Jianping Zhao
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
| | - Weining Xiong
- Department of Respiratory and Critical Care Medicine, Wuhan Clinical Medical Research Center for Chronic Airway Medicine, NHC Key Laboratory of Pulmonary Diseases, Key cite of National Clinical Research Center for Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, 1095 Jiefang Ave, Wuhan, 430030, China. .,Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Lu, Shanghai, 200011, China.
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27
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Chen H, Wang K, Pei D, Xu H. Appraising circular RNAs as novel biomarkers for the diagnosis and prognosis of gastric cancer: A pair-wise meta-analysis. J Clin Lab Anal 2020; 34:e23303. [PMID: 32196751 PMCID: PMC7439415 DOI: 10.1002/jcla.23303] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/21/2020] [Accepted: 02/22/2020] [Indexed: 12/24/2022] Open
Abstract
Background Circular RNAs (circRNAs), proven as single‐stranded closed RNA molecules, have been implicated in the onset and development of multiple cancers. This study aimed to summarize existing evidences regarding the clinicopathologic, diagnostic, and prognostic significances of circRNAs in gastric cancer (GC). Methods Eligible studies were identified using online databases. The quality of the included studies was judged, and patients' clinical characteristics, diagnostic data, and overall survival (OS) were extracted from the electronic medical record. Fisher's method was adopted to determine P values for clinicopathologic features. The diagnostic and prognostic data from all included studies were merged. Results Thirty eligible studies were comprised of 2687 GC patients were enrolled in the meta‐analyses. Altered expressions of circRNAs in GC tissues were significantly associated with worse clinicopathologic features. Abnormally expressed circRNAs yielded a pooled sensitivity of 0.76 (95% CI: 0.69‐0.81) and a specificity of 0.77 (95% CI: 0.70‐0.83) in distinguishing GC from noncancerous controls, which corresponded to an area under the curve (AUC) of 0.83. The survival analysis showed that the oncogenic circRNA signature could be an independent risk factor of OS (HR = 2.11, 95% CI: 1.60‐2.78, P = .000). Patients with down‐regulated circRNAs (tumor suppressor genes) presented a significantly shorter OS time than those with high‐level circRNAs (HR = 0.33, 95% CI: 0.27‐0.42, P = .000). Stratified analyses based on sample type, control source, circRNA expression status, and cutoff setting also produced robust results. Conclusions CircRNAs may play an important role as potential diagnostic and prognostic biomarkers of GC.
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Affiliation(s)
- Hongjun Chen
- Department of Clinical Laboratory, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, China
| | - Kun Wang
- Department of Clinical Laboratory, Huanghe Sanmenxia Hospital, Sanmenxia, China
| | - Dongxu Pei
- Department of Clinical Laboratory, Henan Province Hospital of TCM, Zhengzhou, China
| | - Haisheng Xu
- Department of Clinical Laboratory, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, China
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28
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Wang N, Lu K, Qu H, Wang H, Chen Y, Shan T, Ge X, Wei Y, Zhou P, Xia J. CircRBM33 regulates IL-6 to promote gastric cancer progression through targeting miR-149. Biomed Pharmacother 2020; 125:109876. [PMID: 32044717 DOI: 10.1016/j.biopha.2020.109876] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/16/2022] Open
Abstract
There is increasing evidence of the vital role played by circular RNAs (circRNAs) in the progression of gastric cancer (GC). A circRNA, hsa_circ_0001772, was generated from the RBM33 gene and named circRBM33. The aim of this study was to investigate the role of circRBM33 in GC. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of circRBM33 in 79 pairs of GC tissues and paracancerous tissues and 4 GC cell lines (MGC-803, BGC-823, SGC-7901, and AGS). Bioinformatics databases were used to predict downstream targets of circRNA and micro RNA (miRNA). Dual luciferase reporter assay was used to verify whether miR-149 was a direct binding target for circRBM33. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2´-deoxyuridine (EDU) assay, transwell assay, and flow-cytometric analyses were performed to determine the role of circRBM33 in the biological functioning of GC cells. Western blot technique was used to quantify the levels of interleukin-6 (IL-6). CircRBM33 was distinctly upregulated in GC specimens and cell lines and a close correlation between circRBM33 expression and clinical characteristics of GC was observed. After silencing circRBM33, the apoptosis of GC cells increased, while proliferation, migration, and invasion decreased. Rescue experiments indicated that circRBM33 manipulates biological function in GC cells through the circRBM33/miR-149/IL-6 axis. CircRBM33 can be used as a tumor biomarker and a possible therapeutic target in the future.
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Affiliation(s)
- Ning Wang
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Keyu Lu
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Huiheng Qu
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Hao Wang
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Yigang Chen
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Ting Shan
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Xuhui Ge
- Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yunyu Wei
- Department of Laboratory, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Peng Zhou
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Jiazeng Xia
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China.
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29
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Naeli P, Pourhanifeh MH, Karimzadeh MR, Shabaninejad Z, Movahedpour A, Tarrahimofrad H, Mirzaei HR, Bafrani HH, Savardashtaki A, Mirzaei H, Hamblin MR. Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role. Crit Rev Oncol Hematol 2020; 145:102854. [PMID: 31877535 PMCID: PMC6982584 DOI: 10.1016/j.critrevonc.2019.102854] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 11/28/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Both environmental and genetic factors are involved in the initiation and development of gastrointestinal cancer. Covalent closed circular RNAs (circRNAs) are produced by a mechanism called "back-splicing" from mRNAs. They are highly stable and show cell and tissue specific expression patterns. Although some functions such as "microRNA sponge" and "RNA binding protein sponge" have been reported for a small number of circRNAs, the function of thousands of other circRNAs is still unknown. Dysregulation of circRNAs has been reported in many GI cancers and are involved in metastasis and invasion. CircRNAs have been reported to be useful as prognostic markers and targets for developing new treatments. We first describe the properties and biogenesis of circRNAs. We then summarize recent reports about circRNA functions, expression status, and their potential to be used as biomarkers in GI cancers including, gastric cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, gallbladder cancer and pancreatic cancer.
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Affiliation(s)
- Parisa Naeli
- Department of Biological Sciences, Faculty of Genetics, Tarbiat Modares University, Tehran, Iran.
| | | | - Mohammad Reza Karimzadeh
- Department of Medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, Iran.
| | - Zahra Shabaninejad
- Department of Nanobiotechnology, School of Basic Sciences, TarbiatModares University, Tehran, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Hossein Tarrahimofrad
- Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
| | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hassan Hassani Bafrani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| | - Amir Savardashtaki
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences Shiraz, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA.
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30
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Tang X, Zhu J, Liu Y, Chen C, Liu T, Liu J. Current Understanding of Circular RNAs in Gastric Cancer. Cancer Manag Res 2019; 11:10509-10521. [PMID: 31853202 PMCID: PMC6916696 DOI: 10.2147/cmar.s223204] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 11/15/2019] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Advanced diagnosis and high rates of relapse and metastasis are associated with the poor prognosis of this disease. GC has a complex etiopathogenesis of which the underlying mechanisms remain to be explored. Studies on circular RNAs (circRNAs), noncoding RNAs that may be potential targets in GC, have made substantial progress over the past few years. CircRNAs exert important effects on the onset and progression of GC. Hence, this article aims to summarize the findings of recent studies of circRNAs related to GC and to describe the underlying mechanisms and potential applications. The findings indicate that circRNAs participate in GC regulation, proliferation, invasion, and metastasis through regulating microRNAs, proteins, genes, and signaling pathways. In addition, dysregulated circRNAs may be used as novel diagnostic and prognostic biomarkers or therapeutic targets. This review is expected to facilitate a better understanding of GC, and it suggests novel circRNA-based methods to inhibit or prevent GC.
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Affiliation(s)
- Xiaohuan Tang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Jiaming Zhu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Yuanda Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Chao Chen
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Tianzhou Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Jingjing Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
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31
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Li YF, Zhang J, Yu L. Circular RNAs Regulate Cancer Onset and Progression via Wnt/β-Catenin Signaling Pathway. Yonsei Med J 2019; 60:1117-1128. [PMID: 31769242 PMCID: PMC6881706 DOI: 10.3349/ymj.2019.60.12.1117] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 10/04/2019] [Accepted: 10/15/2019] [Indexed: 12/12/2022] Open
Abstract
Cancer remains to be a major challenge for public health providers, and is the second leading cause of death worldwide. Therefore, it is imperative to explore the mechanisms underlying cancer initiation and development, and design novel diagnostics and therapeutics. Circular RNAs (circRNAs), which exhibit a covalently closed loop structure, are involved in a variety of diseases, including cancer. The aberrant expression of circRNAs contributes to the initiation and development of various cancers by disrupting the interplay of specific signaling pathways, including the Wnt/β-catenin pathway, which controls a plethora of cellular processes that drive cancer development. The interactions between circRNAs (specifically expressed in different cancer tissues) and Wnt/β-catenin signaling pathway presents potential diagnostic biomarkers and novel therapeutic targets. In this review, we have summarized research discoveries on the functions of Wnt/β-catenin pathway-related circRNAs in the modulation of oncogenesis and progression of different types of cancer. We anticipate that our findings will contribute to the improvement or development of circRNAs-based strategies for cancer treatment.
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Affiliation(s)
- Yun Feng Li
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Jian Zhang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Lei Yu
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China.
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32
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Wang Y, Juan L, Peng J, Zang T, Wang Y. Prioritizing candidate diseases-related metabolites based on literature and functional similarity. BMC Bioinformatics 2019; 20:574. [PMID: 31760947 PMCID: PMC6876110 DOI: 10.1186/s12859-019-3127-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background As the terminal products of cellular regulatory process, functional related metabolites have a close relationship with complex diseases, and are often associated with the same or similar diseases. Therefore, identification of disease related metabolites play a critical role in understanding comprehensively pathogenesis of disease, aiming at improving the clinical medicine. Considering that a large number of metabolic markers of diseases need to be explored, we propose a computational model to identify potential disease-related metabolites based on functional relationships and scores of referred literatures between metabolites. First, obtaining associations between metabolites and diseases from the Human Metabolome database, we calculate the similarities of metabolites based on modified recommendation strategy of collaborative filtering utilizing the similarities between diseases. Next, a disease-associated metabolite network (DMN) is built with similarities between metabolites as weight. To improve the ability of identifying disease-related metabolites, we introduce scores of text mining from the existing database of chemicals and proteins into DMN and build a new disease-associated metabolite network (FLDMN) by fusing functional associations and scores of literatures. Finally, we utilize random walking with restart (RWR) in this network to predict candidate metabolites related to diseases. Results We construct the disease-associated metabolite network and its improved network (FLDMN) with 245 diseases, 587 metabolites and 28,715 disease-metabolite associations. Subsequently, we extract training sets and testing sets from two different versions of the Human Metabolome database and assess the performance of DMN and FLDMN on 19 diseases, respectively. As a result, the average AUC (area under the receiver operating characteristic curve) of DMN is 64.35%. As a further improved network, FLDMN is proven to be successful in predicting potential metabolic signatures for 19 diseases with an average AUC value of 76.03%. Conclusion In this paper, a computational model is proposed for exploring metabolite-disease pairs and has good performance in predicting potential metabolites related to diseases through adequate validation. This result suggests that integrating literature and functional associations can be an effective way to construct disease associated metabolite network for prioritizing candidate diseases-related metabolites.
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Affiliation(s)
- Yongtian Wang
- School of Computer Science and Technology, Harbin Institute of Technology, Harbin, 150001, People's Republic of China
| | - Liran Juan
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, People's Republic of China
| | - Jiajie Peng
- School of Computer Science, Northwestern Polytechnical University, Xi'an, People's Republic of China
| | - Tianyi Zang
- School of Computer Science and Technology, Harbin Institute of Technology, Harbin, 150001, People's Republic of China.
| | - Yadong Wang
- School of Computer Science and Technology, Harbin Institute of Technology, Harbin, 150001, People's Republic of China.
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33
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Fang X, Wen J, Sun M, Yuan Y, Xu Q. CircRNAs and its relationship with gastric cancer. J Cancer 2019; 10:6105-6113. [PMID: 31762820 PMCID: PMC6856571 DOI: 10.7150/jca.32927] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 08/18/2019] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs), as a type of tissue specific RNA with more stable structure than linear RNAs, was poorly understood on its correlation with gastric cancer (GC). In this review, we outline the synthesis and characteristics of circRNAs and generalize their categories and functions. Through comprehensive analysis of the reported results, we find that circRNAs not only participate in the regulation of gastric cancer (GC) cell biological behaviors, such as proliferation, invasion, migration and epithelial mesenchymal transition (EMT), but also are related to the clinicopathological features of GC such as tumor differentiation, TNM stage and metastasis, etc. According to the present screening and verification results, circRNAs are suggested to be used as biomarkers for the early diagnosis and prognosis prediction of GC, and those circRNAs involved in the genesis and development of GC have the potential as novel targets for the individualized treatment of GC.
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Affiliation(s)
- Xinxin Fang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
| | - Jing Wen
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
| | - Mingjun Sun
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China.,Key Laboratory of Gastrointestinal Cancer Etiology and Screening, Liaoning Province, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Key Laboratory of Gastrointestinal Cancer Etiology and Screening, Liaoning Province, Shenyang 110001, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Key Laboratory of Gastrointestinal Cancer Etiology and Screening, Liaoning Province, Shenyang 110001, China
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Shan C, Zhang Y, Hao X, Gao J, Chen X, Wang K. Biogenesis, functions and clinical significance of circRNAs in gastric cancer. Mol Cancer 2019; 18:136. [PMID: 31519189 PMCID: PMC6743094 DOI: 10.1186/s12943-019-1069-0] [Citation(s) in RCA: 172] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/06/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumours in the world and has high morbidity and mortality. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently linked circular structures. In recent years, plentiful circRNAs have been discovered that participate in many biological processes, including the initiation and development of tumours. Increasing evidences suggest important biological functions of circRNAs, implying that circRNAs may serve as vital new biomarkers and targets for disease diagnosis and prognosis. Among these, circRNAs are tend to aberrantly expressed and are regarded as potential biomarkers in the carcinogenesis and progression of GC. This review systematically summarised the biogenesis, biological properties and functions of circRNAs, with a focus on their relationship with GC, as well as their probable clinical implications on GC. As our cognition of the relation between circRNAs and GC deepens, more molecular mechanisms of GC progression will be discovered, and new therapeutic strategies will be used for the prevention and treatment of GC.
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Affiliation(s)
- Chan Shan
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
| | - Yinfeng Zhang
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Xiaodan Hao
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Jinning Gao
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Xinzhe Chen
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Kun Wang
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
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Wang Y, Nie C, Zang T, Wang Y. Predicting circRNA-Disease Associations Based on circRNA Expression Similarity and Functional Similarity. Front Genet 2019; 10:832. [PMID: 31572444 PMCID: PMC6751509 DOI: 10.3389/fgene.2019.00832] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 08/13/2019] [Indexed: 12/19/2022] Open
Abstract
Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that have well-conserved sequences. Emerging evidence has shown that circRNAs can be novel biomarkers or therapeutic targets for many diseases and play an important role in the development of various pathological conditions. Therefore, identifying potential disease-related circRNAs is helpful in improving the efficiency of finding therapeutic targets for diseases. Here, we propose a computational model (PreCDA) to predict potential circRNA-disease associations. First, we calculated the circRNA expression similarity based on circRNA expression profiles. The circRNA functional similarity is calculated based on cosine similarity, and the disease similarity is used as the dimension of each circRNA vector. The associations between circRNAs and diseases are defined based on the circRNA functional similarity and expression similarity. We constructed a disease-related circRNA association network and used a graph-based recommendation algorithm (PersonalRank) to sort candidate disease-related circRNAs. As a result, PreCDA has an average area under the receiver operating characteristic curve value of 78.15% in predicting candidate disease-related circRNAs. In addition, we discuss the factors that affect the performance of this method and find some unknown circRNAs related to diseases, with several common diseases used as case studies. These results show that PreCDA has good performance in predicting potential circRNA-disease associations and is helpful for the diagnosis and treatment of human diseases.
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Affiliation(s)
| | | | - Tianyi Zang
- School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yadong Wang
- School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China
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Li J, Li H, Lv X, Yang Z, Gao M, Bi Y, Zhang Z, Wang S, Cui Z, Zhou B, Yin Z. Diagnostic performance of circular RNAs in human cancers: A systematic review and meta-analysis. Mol Genet Genomic Med 2019; 7:e00749. [PMID: 31106993 PMCID: PMC6625099 DOI: 10.1002/mgg3.749] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 02/26/2019] [Accepted: 04/26/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Recently, accumulating evidence have revealed that circular RNA (circRNA) was deregulated in multiple types of cancer, suggesting that circRNA might serve as a novel candidate biomarker of cancer diagnosis. However, inconsistent results have become an obstacle in applying circRNAs to clinical practice. The aim of this study is to evaluate diagnostic value of circRNAs among cancers. METHODS A literature search was systematically performed among PubMed, Sciencedirect, Cochrane Library, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases up to February 15, 2019. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratios, negative likelihood ratios, diagnostic odds ratio, and area under the SROC curve (AUC) were applied to evaluate diagnostic performance of circRNAs. RESULTS In total, the study included 64 studies with single circRNA and 13 studies with combined circRNAs. Overall, the study presented that a single circRNA had moderate diagnostic value, with a SEN of 0.75, a SPE of 0.76, and an AUC of 0.82. The plasma circRNAs had higher diagnostic accuracy than tissue (AUC: 0.87, 95% confidence interval [CI]: 0.83-0.89 for plasma/serum subgroup; AUC: 0.79, 95% CI: 0.75-0.82 for tissue subgroup). Furthermore, the combined circRNAs had good diagnostic efficacy for GC, with a SEN of 0.89, a SPE of 0.94, and an AUC of 0.97, respectively. CONCLUSION This study confirmed that circRNAs may be candidate biomarkers for cancer diagnosis. In particular, diagnosis of combined circRNAs will be a new alternative applied to clinical research and practice for cancer.
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Affiliation(s)
- Juan Li
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Hang Li
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Xiaoting Lv
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Zitai Yang
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Min Gao
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Yanhong Bi
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Ziwei Zhang
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Shengli Wang
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Zhigang Cui
- School of NursingChina Medical UniversityShenyangChina
| | - Baosen Zhou
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
| | - Zhihua Yin
- Department of Epidemiology, School of Public HealthChina Medical UniversityShenyangPR China
- Key Laboratory of Cancer Etiology and InterventionUniversity of Liaoning ProvinceShenyangPR China
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Wang KW, Dong M. Role of circular RNAs in gastric cancer: Recent advances and prospects. World J Gastrointest Oncol 2019; 11:459-469. [PMID: 31236197 PMCID: PMC6580317 DOI: 10.4251/wjgo.v11.i6.459] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 04/06/2019] [Accepted: 04/19/2019] [Indexed: 02/05/2023] Open
Abstract
Circular RNA (circRNA) is a newly discovered non-coding RNA with special structure, which is widely expressed in eukaryotic organisms and mainly located in the cytoplasm. circRNAs participate in gene regulation by working as miRNA sponges that block the inhibitory effect of miRNA on its target genes. In addition, circRNAs can bind to RNA binding proteins to regulate gene expression. Based on characteristics of stability, expression specificity and participation in gene regulation, circRNAs are expected to be biomarkers for early diagnosis of cancer or potential targets for cancer therapy. With the help of bioinformatics analysis, circRNA microarray analysis and high-throughput sequencing technology, more circRNAs were discovered to participate in the progression of gastric cancer (GC) over the past three years. This article gives an overview of these recent research focusing on the roles of circRNAs in GC and highlights the advances.
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Affiliation(s)
- Ke-Wei Wang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Ming Dong
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Necula L, Matei L, Dragu D, Neagu AI, Mambet C, Nedeianu S, Bleotu C, Diaconu CC, Chivu-Economescu M. Recent advances in gastric cancer early diagnosis. World J Gastroenterol 2019; 25:2029-2044. [PMID: 31114131 PMCID: PMC6506585 DOI: 10.3748/wjg.v25.i17.2029] [Citation(s) in RCA: 289] [Impact Index Per Article: 48.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/03/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.
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Affiliation(s)
- Laura Necula
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
- Faculty of Medicine, Titu Maiorescu University, Bucharest 040441, Romania
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Denisa Dragu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Ana I Neagu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Cristina Mambet
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Saviana Nedeianu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Coralia Bleotu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Carmen C Diaconu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Mihaela Chivu-Economescu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
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Circular RNAs as diagnostic biomarkers in gastric cancer: A meta-analysis review. Pathol Res Pract 2019; 215:152419. [PMID: 31043351 DOI: 10.1016/j.prp.2019.04.011] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 04/03/2019] [Accepted: 04/16/2019] [Indexed: 12/14/2022]
Abstract
PURPOSE Gastric cancer is a malignant tumor in the world and circRNA has a close connection with it. However, the effects of circRNA on gastric cancer is still not clear. METHODS A comprehensive search of PubMed, Web of Science and Embase for published experimental studies about circRNA from 2013 to June 2018 was conducted with two investigators. Diagnostic OR (DOR) was calculated to evaluate the diagnostic efficacy by STATA 12.0. RESULTS Total 11 studies were found, including 12 kinds of circRNAs, 11 in tissues, 5 in plasma, and all down regulated. The combined DOR and AUC (Area Under the Curve of Receiver Operating Characteristic) with their 95%CI were 8.778 [6.108, 12.614] and 0.81 [0.78, 0.84] respectively, indicating that circRNAs can reflect gastric cancer as well. Subgroup analysis revealed that circRNAs in plasma were higher than tissues as well as in subgroup with different sample sizes. We speculated that the heterogeneity of the literatures was mainly due to the different backgrounds of gastric cancer and the differences in experimental design and operation process. And the Deeks' funnel map revealed there was no obvious public biasness in the literature. CONCLUSION CircRNAs have high sensitivity and specificity in the diagnosis of gastric cancer, and it may become an auxiliary diagnostic biomarker of gastric cancer.
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Tan H, Gan L, Fan X, Liu L, Liu S. Diagnostic value of circular RNAs as effective biomarkers for cancer: a systematic review and meta-analysis. Onco Targets Ther 2019; 12:2623-2633. [PMID: 31114221 PMCID: PMC6497823 DOI: 10.2147/ott.s197537] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Accepted: 02/27/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Increasing evidence has identified circular RNAs (circRNAs) as ideal molecular biomarkers for cancer diagnosis, therapy, and prognosis. However, the overall diagnostic efficiency of circRNAs remains unclear. Thus, this meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of circRNA expression profiles for cancer. Methods: A literature search of online databases was conducted to identify all eligible studies. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All statistical analyses were executed using STATA 14.0, Meta-DiSc 1.4, and Review Manager 5.2 software. Results: A total of 32 studies, involving 2,400 cases and 2,295 controls, were included in the diagnostic meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.79 (95% CI: 0.73–0.84), 0.73 (95% CI: 0.67–0.79), 2.9 (95% CI: 2.5–3.5), 0.29 (95% CI: 0.24–0.36), 10 (95% CI: 8–13), and 0.83 (95% CI: 0.79–0.86), respectively. The overall analysis suggested that circRNAs are useful diagnostic biomarkers for cancer. Subgroup analysis indicated that plasma samples had a better diagnostic performance than cancer tissue samples for cancer detection. Studies involving ≥100 cases or gastric cancer showed higher sensitivities than those including <100 cases or other cancers. Conclusion: This meta-analysis revealed that circRNAs were significantly correlated with cancer diagnosis. In addition, circRNAs had good diagnostic accuracy and might serve as effective diagnostic biomarkers for cancer.
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Affiliation(s)
- Hong Tan
- Department of General Surgery, Chengdu Integrated TCM & Western Medicine Hospital (Chengdu First People's Hospital), Chengdu, 610041, China
| | - Li Gan
- School of Medicine, University of Electronic Science and Technology of China, Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610054, China
| | - Xiaoming Fan
- Department of Laboratory Medicine, Affiliated Hospital of University of Electronic Science and Technology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, China
| | - Limin Liu
- Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochou University, Institute of Blood and Marrow Transplantation, Suzhou, 215006, China
| | - Shan Liu
- Department of Laboratory Medicine, Affiliated Hospital of University of Electronic Science and Technology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, China
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circSMARCA5 Functions as a Diagnostic and Prognostic Biomarker for Gastric Cancer. DISEASE MARKERS 2019; 2019:2473652. [PMID: 30956729 PMCID: PMC6431400 DOI: 10.1155/2019/2473652] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 12/10/2018] [Accepted: 01/03/2019] [Indexed: 12/14/2022]
Abstract
Background Circular RNAs have been implicated in various malignancies and can function as potential biomarkers for cancers. Reportedly, circSMARCA5 was downregulated in hepatocellular carcinoma and glioblastoma multiforme, but upregulated in prostate cancer. The functional roles and clinical significance of circSMARCA5 still remain unknown in the context of gastric cancer (GC). Methods Expression levels of circSMARCA5 were detected by qRT-PCR. Clinical data including patient basic information, clinicopathological features, and survival data were obtained. The Kaplan-Meier methods, multivariate Cox regression models, and the receiver operating characteristic curve were used to assess the clinical significance of circSMARCA5 in GC. Cell proliferation assays and transwell assays were performed to elucidate the functional roles of circSMARCA5 in GC. Results The circSMARCA5 level was decreased in GC tissues and cell lines. The low expression level of circSMARCA5 was correlated to poorer overall survival and disease-free survival. Low circSMARCA5 expression was revealed as an independent unfavorable predictive factor for GC. The results indicated that circSMARCA5 had a moderate ability for discrimination between GC patients and controls with an area under the curve of 0.806. Upregulation of circSMARCA5 dampened the proliferation, migration, and invasion of GC cells, whereas circSMARCA5 knockdown promoted GC progression. Discussion Our results demonstrated that circSMARCA5 was decreased and exerted tumor-suppressive effects in GC. circSMARCA5 can function as a potential biomarker for GC prognosis and diagnosis.
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Xu JZ, Shao CC, Wang XJ, Zhao X, Chen JQ, Ouyang YX, Feng J, Zhang F, Huang WH, Ying Q, Chen CF, Wei XL, Dong HY, Zhang GJ, Chen M. circTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis. Cell Death Dis 2019; 10:175. [PMID: 30787278 PMCID: PMC6382814 DOI: 10.1038/s41419-019-1382-y] [Citation(s) in RCA: 203] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 01/09/2019] [Accepted: 01/17/2019] [Indexed: 02/05/2023]
Abstract
More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.
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Affiliation(s)
- Jian-Zhen Xu
- Department of Bioinformatics, Shantou University Medical College (SUMC), 515041, Shantou, China.
| | - Chang-Chun Shao
- ChangJiang Scholar's Laboratory, Shantou University Medical College, 515041, Shantou, China
| | - Xiao-Jia Wang
- Key Lab of Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, 310000, Hangzhou, China
| | - Xing Zhao
- Department of Bioinformatics, Shantou University Medical College (SUMC), 515041, Shantou, China
| | - Jun-Qing Chen
- Key Lab of Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, 310000, Hangzhou, China
| | - Yan-Xiu Ouyang
- ChangJiang Scholar's Laboratory, Shantou University Medical College, 515041, Shantou, China
| | - Jun Feng
- ChangJiang Scholar's Laboratory, Shantou University Medical College, 515041, Shantou, China
| | - Fan Zhang
- Guangdong Provincial Key Laboratory on Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, 515041, Shantou, China
| | - Wen-He Huang
- The Breast Center, Cancer Hospital of Shantou University Medical College, 515041, Shantou, China
| | - Qian Ying
- Key Lab of Diagnosis & Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, 310000, Hangzhou, China
| | - Chun-Fa Chen
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China
| | - Xiao-Long Wei
- Department of Pathology, Cancer Hospital of Shantou University Medical College, 515041, Shantou, China
| | - Hong-Yan Dong
- Department of Pathology, Linyi People's Hospital, 276000, Linyi, China
| | - Guo-Jun Zhang
- ChangJiang Scholar's Laboratory, Shantou University Medical College, 515041, Shantou, China.
- The Breast Center, Cancer Hospital of Shantou University Medical College, 515041, Shantou, China.
- The Cancer Center, Xiang'an Hospital of Xiamen University, 2000 Xiang'an East Rd., 361111, Xiamen, Fujian, China.
| | - Min Chen
- ChangJiang Scholar's Laboratory, Shantou University Medical College, 515041, Shantou, China.
- The Cancer Center, Xiang'an Hospital of Xiamen University, 2000 Xiang'an East Rd., 361111, Xiamen, Fujian, China.
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Yan L, Zheng M, Wang H. Circular RNA hsa_circ_0072309 inhibits proliferation and invasion of breast cancer cells via targeting miR-492. Cancer Manag Res 2019; 11:1033-1041. [PMID: 30774431 PMCID: PMC6349082 DOI: 10.2147/cmar.s186857] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Background Although the number of circular RNAs (circRNAs) that has been identified in multiple cancer tissues continues to increase, the relationship between circRNA expression and carcinogenesis remains unknown. The role of hsa_circ_0072309 in breast cancer has remained undefined until now. In this study, we aimed to investigate the role of hsa_circ_0072309 in breast cancer progression. Methods hsa_circ_0072309 expression in breast cancer tissues was analyzed using qRT-PCR. A series of functional experiments were carried out to investigate hsa_circ_0072309 function in breast cancer development and its underlying molecular mechanisms. Results hsa_circ_0072309 expression in breast cancer tissues was upregulated relative to that in adjacent normal tissues. hsa_circ_0072309 could serve as a prognostic biomarker of breast cancer. hsa_circ_0072309 overexpression dramatically inhibited the proliferation, migration, and invasion of breast cancer cells in vitro. In vivo assays revealed that the ectopic expression of hsa_circ_0072309 repressed breast cancer growth. The results of our mechanistic studies indicated that hsa_circ_0072309 could act as the sponge of miR-492, which exhibited increased expression in breast cancer tissues. Hsa_circ_0072309 suppressed breast cancer cell proliferation, migration, and invasion by inhibiting miR-492. Conclusion Our findings revealed for the first time that the hsa_circ_0072309-miR-492 axis plays an essential role in breast cancer progression.
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Affiliation(s)
- Lin Yan
- Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Min Zheng
- Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Hua Wang
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China,
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Zheng S, Gu T, Bao X, Sun J, Zhao J, Zhang T, Zhang L. Circular RNA hsa_circ_0014243 may serve as a diagnostic biomarker for essential hypertension. Exp Ther Med 2018; 17:1728-1736. [PMID: 30783441 PMCID: PMC6364221 DOI: 10.3892/etm.2018.7107] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 11/01/2018] [Indexed: 12/14/2022] Open
Abstract
Circular RNAs (circRNAs) have a great potential as clinical biomarkers; however, specific circRNAs with a diagnostic value for essential hypertension (EH) largely remain to be identified. In the present study, the potential application of Homo sapiens (hsa)_circ_0014243, which was identified to be significantly upregulated in whole blood samples of EH patients in a previous microarray profiling study by our group, in the diagnosis of EH was evaluated. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the expression levels of hsa_circ_0014243 and hsa-microRNA (miR)-10a-5p in a total of 178 blood samples collected from 89 healthy controls and 89 patients diagnosed with EH. Divergent primers were designed for circRNAs, while conventional primers were used for miRs. Independent-samples t-tests and bivariate correlation analyses were performed to analyze the association between clinical factors influencing EH and hsa_circ_0014243 expression levels. A receiver operating characteristics (ROC) curve was generated to estimate the diagnostic value of hsa_circ_0014243 for EH. Finally, the expression levels of circRNAs and miRNAs were combined to propose a possible prediction model for EH. The results indicated that hsa_circ_0014243 was upregulated in whole blood samples of EH patients compared with that in the controls (P<0.001). Furthermore, the relative expression levels of hsa_circ_0014243 (Δ quantification cycle) were identified to be significantly correlated with age (r=-0.259, P<0.001), high-density lipoprotein levels (r=0.196, P=0.009) and glucose levels (r=-0.204, P=0.006). The area under the ROC curve (AUC) of the model using hsa_circ_0014243 as a predictor was 0.732. Of note, the AUC increased to 0.781 when hsa_circ_0014243 levels were combined with hsa-miR-10a-5p levels as predictors. The present results suggest that hsa_circ_0014243 has a crucial role in the genesis and development of EH, and presents a certain diagnostic capability for EH.
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Affiliation(s)
- Shuying Zheng
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Tianlun Gu
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Xingjie Bao
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Jihan Sun
- Department of Clinical Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P.R. China
| | - Jinshun Zhao
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Tao Zhang
- Department of Chronic Disease Control and Prevention, Ningbo Municipal Center for Disease Control and Prevention, Ningbo, Zhejiang 315000, P.R. China
| | - Lina Zhang
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
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Ouyang Y, Li Y, Huang Y, Li X, Zhu Y, Long Y, Wang Y, Guo X, Gong K. CircRNA circPDSS1 promotes the gastric cancer progression by sponging miR-186-5p and modulating NEK2. J Cell Physiol 2018; 234:10458-10469. [PMID: 30417526 DOI: 10.1002/jcp.27714] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 10/15/2018] [Indexed: 12/17/2022]
Abstract
The aim of this study is to investigate the regulatory mechanism of circPDSS1/miR-186-5p/NEK2 axis on the viability and proliferation in gastric cancer (GC) cell line. Differentially expressed circRNAs, miRNAs, and mRNAs in GC tissues and paracarcinoma tissues were analyzed using gene chips GSE83521, GSE89143, and GSE93415. Then, the expression of circPDSS1, miR-186-5p, and NEK2 was analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis was adopted to explore the association between the circPDSS1 expression and the prognosis of GC. The effect of circPDSS1 on GC cell cycle and apoptosis was verified with the flow cytometry. Targeting relationships among circPDSS1, miR-186-5p, and NEK2 were predicted via bioinformatics analysis and demonstrated by the dual-luciferase reporter assay. Our results showed that circPDSS1 and NEK2 were high-expressed whereas miR-186-5p was low-expressed in GC tissues and cells. CircPDSS1 promoted GC cell cycle and inhibited apoptosis by sponging miR-186-5p, while miR-186-5p inhibited cell cycle and promoted apoptosis by targeting NEK2. Thus, circPDSS1 acts as a tumor promoter by regulating miR-186-5p and NEK2, which could be a potential biomarker and therapeutic target for the management of GC.
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Affiliation(s)
- Yiming Ouyang
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Yuejin Li
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Yingguang Huang
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Xing Li
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Yu Zhu
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Yaxin Long
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Yongzhi Wang
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Xiaodong Guo
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
| | - Kunmei Gong
- Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China
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Wang L, Shen J, Jiang Y. Circ_0027599/PHDLA1 suppresses gastric cancer progression by sponging miR-101-3p.1. Cell Biosci 2018; 8:58. [PMID: 30410722 PMCID: PMC6219040 DOI: 10.1186/s13578-018-0252-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 10/03/2018] [Indexed: 12/17/2022] Open
Abstract
Background Pleckstrin homology-like domain family A member 1 (PHLDA1) is a tumor suppressor gene in gastric cancer, but its role regulated by circular RNAs (circRNAs) is not known. CircRNAs are important regulators in cancer growth and progression, however, the molecular roles of circRNAs in gastric cancer are rarely known. The study was aimed to investigate the role of circRNAs in regulating PHLDA1 expression in gastric cancer. Results The circRNA expression profile in the gastric cancer tissues by circRNA microarray showed that hsa_circ_0027599 (circ_0027599) was significantly down-regulated in gastric cancer patients and cells when comparing with the controls. Circ_0027599 overexpression suppressed gastric cancer cell proliferation and metastasis. By using bioinformatics tools and luciferase reporter assays, circ_0027599 was verified as a sponge of miR-101-3p.1 (miR-101) and suppressed cancer cell survival and metastasis. It was also verified that PHLDA1 was regulated by circ_0027599 in gastric cancer cells. Conclusions The study uncovered that PHLDA1 was regulated by circ_0027599/miR-101, which suppressed gastric cancer survival and metastasis in gastric cancer.
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Affiliation(s)
- Liang Wang
- Department of Gastroenterology, Shanghai Jinshan Branch of the Sixth People's Hospital, 147 Health Road, Zhujing Town, Jinshan District, Shanghai, 201500 China
| | - Jingyan Shen
- Department of Gastroenterology, Shanghai Jinshan Branch of the Sixth People's Hospital, 147 Health Road, Zhujing Town, Jinshan District, Shanghai, 201500 China
| | - Yushan Jiang
- Department of Gastroenterology, Shanghai Jinshan Branch of the Sixth People's Hospital, 147 Health Road, Zhujing Town, Jinshan District, Shanghai, 201500 China
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Yang R, Xu B, Yang B, Fu J, Liu L, Amjad N, Cai A, Tan C, Chen H, Wang X. Circular RNA Transcriptomic Analysis of Primary Human Brain Microvascular Endothelial Cells Infected with Meningitic Escherichia coli. MOLECULAR THERAPY-NUCLEIC ACIDS 2018; 13:651-664. [PMID: 30497055 PMCID: PMC6258830 DOI: 10.1016/j.omtn.2018.10.013] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 09/20/2018] [Accepted: 10/20/2018] [Indexed: 01/16/2023]
Abstract
With their essential regulatory roles in gene expression and high abundance in the brain, circular RNAs (circRNAs) have recently attracted considerable attention. Many studies have shown that circRNAs play important roles in the pathology of CNS diseases, but whether circRNAs participate in E. coli-induced bacterial meningitis is unclear. We used high-throughput sequencing to analyze the transcriptional profiles of host circRNAs in primary brain microvascular endothelial cells in response to meningitic E. coli. A total of 308 circRNAs were significantly altered, including 140 upregulated and 168 downregulated ones (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology enrichment of the parental genes of these altered circRNAs indicated that they are likely to be involved in diverse biological processes via influencing the expression of their parental genes. Coupled with our previous mRNA and microRNA sequencing data, a competing endogenous RNA analysis was performed, and the potential regulatory network was preliminarily constructed and validated. By revealing the transcriptional profiles of the host circRNAs involved in E. coli meningitis, it is envisaged that the novel insight gained into the regulatory mechanisms of circRNAs in the development of bacterial meningitis will lead to better understanding of how to prevent and treat bacterial CNS infections.
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Affiliation(s)
- Ruicheng Yang
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Bojie Xu
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Bo Yang
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Jiyang Fu
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Lu Liu
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Nouman Amjad
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Aoling Cai
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Chen Tan
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Huanchun Chen
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Xiangru Wang
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
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Zheng SR, Zhang HR, Zhang ZF, Lai SY, Huang LJ, Liu J, Bai X, Ding K, Zhou JY. Human papillomavirus 16 E7 oncoprotein alters the expression profiles of circular RNAs in Caski cells. J Cancer 2018; 9:3755-3764. [PMID: 30405847 PMCID: PMC6216014 DOI: 10.7150/jca.24253] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 04/14/2018] [Indexed: 01/22/2023] Open
Abstract
Cervical cancer is one of the most common cancer in female worldwide. The expression of high-risk human papillomavirus E7 oncogene is necessary for the maintenance of malignant phenotypes and transformation. Accumulating studies of this protein has been explored in cervical cancer, however, there are fewer studies on how E7 expression affects the expression of global circular RNA. CircRNA, a promising biomarker and even therapeutic target, has become a star molecular in research after miRNA and long non-coding RNA. Our aim of this study was to investigate the global circRNA levels modulated by HPV E7 expression and identified the potential consequences for mechanism studies. Here we investigated the expression profiles of circRNAs by transfecting E7 siRNA in Caski cells with high-throughput microarray technology. In total, we identified 526 dysregulated circRNAs with fold change ≥2 or≤0.5, and p< 0.05. Among them, 352 were up-regulated and 174 were down-regulated. In addition, 8 selected circRNAs confirmed using qRT-PCR was in line with the results of microarray analysis. Furthermore, bioinformatic analyses indicated that differently expressed circRNAs might implicate in the mTOR signaling pathway, proline metabolism and glutathione metabolism. In conclusion, this study showed the expression profiles of circRNAs regulated by HPV16 E7 in cervical cancer cells and provides novel insights into the new potential candidates for future mechanism studies.
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Affiliation(s)
- Si-Rong Zheng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Han-Rong Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Zhen-Fei Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Shu-Yu Lai
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Li-Jun Huang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China.,The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Jie Liu
- Department of Gynaecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Xin Bai
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China.,The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Ke Ding
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China.,The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, P.R. China
| | - Jue-Yu Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China
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Hsa_circ_0000673 is down-regulated in gastric cancer and inhibits the proliferation and invasion of tumor cells by targetting miR-532-5p. Biosci Rep 2018; 38:BSR20180538. [PMID: 30061181 PMCID: PMC6146288 DOI: 10.1042/bsr20180538] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 07/13/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022] Open
Abstract
Circular RNAs (circRNAs), a new class of endogenous non-coding RNAs, have recently been known to play critical roles in various cellular biological processes, including tumorigenesis, in which they act as an miRNA sponge that regulates gene expression. Thus, revealing the functions of circRNAs in carcinogenesis and cancer development has been of great interest. However, their expression and functions in gastric cancer (GC) development are still largely unknown. Therefore, the present study aimed to identify novel deregulated circRNAs in GC and reveal their biological functions and molecular mechanisms in GC. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression levels of circRNAs in GC tissues, cell lines, and plasma. The MTT assay, colony formation assay, transwell assay, and tumor xenografts in vivo were used to evaluate the effects of circRNAs on the proliferation and invasion of GC. The abovementioned methods coupled with Western blotting were used to investigate the molecular mechanisms. The current study showed that hsa_circ_0000673 was significantly down-regulated in GC. Overexpression of hsa_circ_0000673 inhibited the proliferation and invasion of GC cells. In contrast, hsa_circ_0000673 down-regulation promoted the proliferation and invasion of GC cells. Further studies revealed that hsa_circ_0000673 targetted miR-532-5p and up-regulated the expression of RUNX3. The present study showed that hsa_circ_0000673 was decreased in GC and it exerted tumor-suppressing effects by targetting miR-532-5p and up-regulating RUNX3 expression level. Hsa_circ_0000673 may be a promising diagnosis biomarker and therapeutic target in GC.
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Xu S, Zhou L, Ponnusamy M, Zhang L, Dong Y, Zhang Y, Wang Q, Liu J, Wang K. A comprehensive review of circRNA: from purification and identification to disease marker potential. PeerJ 2018; 6:e5503. [PMID: 30155370 PMCID: PMC6110255 DOI: 10.7717/peerj.5503] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 08/01/2018] [Indexed: 12/14/2022] Open
Abstract
Circular RNA (circRNA) is an endogenous noncoding RNA with a covalently closed cyclic structure. Based on their components, circRNAs are divided into exonic circRNAs, intronic circRNAs, and exon-intron circRNAs. CircRNAs have well-conserved sequences and often have high stability due to their resistance to exonucleases. Depending on their sequence, circRNAs are involved in different biological functions, including microRNA sponge activity, modulation of alternative splicing or transcription, interaction with RNA-binding proteins, and rolling translation, and are a derivative of pseudogenes. CircRNAs are involved in the development of a variety of pathological conditions, such as cardiovascular diseases, diabetes, neurological diseases, and cancer. Emerging evidence has shown that circRNAs are likely to be new potential clinical diagnostic markers or treatments for many diseases. Here we describe circRNA research methods and biological functions, and discuss the potential relationship between circRNAs and disease progression.
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Affiliation(s)
- Sheng Xu
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - LuYu Zhou
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Murugavel Ponnusamy
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - LiXia Zhang
- Department of Inspection, The Medical Faculty of Qingdao University, Qingdao, Shandong, China
| | - YanHan Dong
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - YanHui Zhang
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Qi Wang
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Jing Liu
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Kun Wang
- Center for Developmental Cardiology, Institute of Translational Medicine and School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
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