Cited by 1,808Circular RNAs in diseasesRNA Research and SplicingCancer-related molecular mechanisms research

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Circular RNA: A new star of noncoding RNAs

Qu, Shibin, Yang, Xisheng, Li, Xiaolei, Wang, Jianlin, Gao, Yuan, Shang, Runze, Sun, Wei, Dou, Kefeng, Li, Haimin·2015·Cancer Letters

DOI 10.1016/j.canlet.2015.06.003

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Abstract

Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. Recent studies have discovered thousands of endogenous circRNAs in mammalian cells. CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins (RBPs) are necessary for circRNA biogenesis. The majority of circRNAs are conserved across species, are stable and resistant to RNase R, and often exhibit tissue/developmental-stage-specific expression. Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression. Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases. Similar to miRNAs and long noncoding RNAs (lncRNAs), circRNAs are becoming a new research hotspot in the field of RNA and could be widely involved in the processes of life. Herein, we review the formation and properties of circRNAs, their functions, and their potential significance in disease.

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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Correction to: CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to enhance the transcriptional activity of β-catenin/LEF1 complex via effects on chromatin remodeling
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Background
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“CircRNAs play a crucial role in disease, especially in cancer, and provide new potential diagnostic and therapeutic targets for disease (Hansen et al., 2013; Qu et al., 2015).”
Background
Quantitative Proteomics Reveals the Regulatory Networks of Circular RNA CDR1as in Hepatocellular Carcinoma Cells
Yang, X. F., Xiong, Q., Wu, Y., Li, S., & Ge, F. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00519 · Cited by 88
Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer
Liang, Y., Song, X., Li, Y., Ma, T., Su, P., Guo, R., Chen, B., Zhang, H., Sang, Y., Liu, Y., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.05.005 · Cited by 88
“Based on the different derivation, circRNAs can be classified into several types, such as exonic, intonic, and intergenic circRNAs.(12,13) Recently, circRNAs have been found to be expressed in various cell lines and species, and they are conserved and highly specific to cell type, tissue, or developmental stage.”
Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway
Cao, J., Zhang, X., Xu, P., Wang, H., Wang, S., Zhang, L., Li, Z., Xie, L., Sun, G., Xia, Y., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01791-9 · Cited by 92
Androgen receptor‐regulated circFNTA activates KRAS signaling to promote bladder cancer invasion
Chen, J., Sun, Y., Ou, Z., Yeh, S., Huang, C., You, B., Tsai, Y., Sheu, T., Zu, X., & Chang, C. (2020) · EMBO Reports · doi:10.15252/embr.201948467 · Cited by 86
“CircRNAs have been shown to be involved in many biological processes, such as miRNA sponging, gene splicing, transcription regulation, and parental gene expression modification [29,30].”
Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p
Xu, Y., Qiu, A., Peng, F., Tan, X., Wang, J., & Gong, X. (2020) · Neoplasma · doi:10.4149/neo_2020_200417n414 · Cited by 87
Hsa_Circ_0001275: A Potential Novel Diagnostic Biomarker for Postmenopausal Osteoporosis
Zhao, K., Zhao, Q., Guo, Z., Chen, Z., Hu, Y., Su, J., Chen, L., He, Z., Cai, X., Chen, M., et al. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000489657 · Cited by 86
Circular RNA hsa_circ_0016070 Is Associated with Pulmonary Arterial Hypertension by Promoting PASMC Proliferation
Zhou, S., Jiang, H., Li, M., Wu, P., Sun, L., Liu, Y., Zhu, K., Zhang, B., Sun, G., Cao, C., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.08.026 · Cited by 86
“It has been shown that circRNAs can act as the sponges of microRNAs (miRNAs) to regulate the expression of their parent genes and, hence, affect the onset and progression of diseases.(13) It has been hypothesized that hsa_circ_0022342 and hsa_circ_0002062 can act as key circRNAs in the onset of chronic thromboembolic…”
Background
Circular RNAs: New Epigenetic Signatures in Viral Infections
Nahand, J. S., Jamshidi, S., Hamblin, M. R., Mahjoubin‐Tehran, M., Vosough, M., Jamali, M., Khatami, A., Moghoofei, M., Baghi, H. B., & Mirzaei, H. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01853 · Cited by 89
Hsa_circ_0006948 enhances cancer progression and epithelial-mesenchymal transition through the miR-490-3p/HMGA2 axis in esophageal squamous cell carcinoma
Pan, Z., Lin, J., Wu, D., He, X., Wang, W., Hu, X., Zhang, L., & Wang, M. (2019) · Aging · doi:10.18632/aging.102519 · Cited by 86
“As a novel non-coding RNA, circular RNA (circRNA) regulates eukaryote gene expression [4, 5].”
Background
A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer
Li, X., Liu, H., Zhou, C., Yang, X., Huang, L., Jie, H., Zeng, Z., Zheng, X., Li, W., Liu, Z., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01773-3 · Cited by 86
“Circular RNAs (circRNAs) are a group of endogenous non-coding RNAs, circularized by a back-splicing reaction [5].”
Background
Circular RNA Expression in Basal Cell Carcinoma
Sand, M. S., Bechara, F. G., Sand, D., Gambichler, T., Hahn, S. A., Bromba, M., Stockfleth, E., & Hessam, S. (2016) · Epigenomics · doi:10.2217/epi-2015-0019 · Cited by 85
Circular RNAs as Promising Biomarkers: A Mini-Review
Abu, N., & Jamal, R. A. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00355 · Cited by 86
Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis
Wu, Z., Shi, W., & Jiang, C. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.184 · Cited by 85
EIF4A3-Induced circ-BNIP3 Aggravated Hypoxia-Induced Injury of H9c2 Cells by Targeting miR-27a-3p/BNIP3
Li, Y., Ren, S., Xia, J., Wei, Y., & Xi, Y. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.11.017 · Cited by 83
Expression profile of circular RNAs in human gastric cancer tissues
Huang, Y., Jie, N., Zou, K., & Weng, Y. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6916 · Cited by 84
Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration
Li, L., Guo, J., Chen, Y., Chang, C., & Xu, C. (2017) · BMC Genomics · doi:10.1186/s12864-016-3476-6 · Cited by 83
“CircRNAs, a novel type of non-coding RNAs, compose a class of RNA developing covalently closed loop structures without 5’–3’ polarities [6] but with widespread, abundant and tissue-specific expression across animals [7].”
Circular RNAs expression profiles in human gastric cancer
Dang, Y., Ouyang, X., Zhang, F., Wang, K., Lin, Y., Sun, B., Wang, Y., Wang, L., & Huang, Q. (2017) · Scientific Reports · doi:10.1038/s41598-017-09076-6 · Cited by 83
A novel circFMN2 promotes tumor proliferation in CRC by regulating the miR-1182/hTERT signaling pathways
Li, Y., Chang-feng, L., Xu, R., Wang, Y., Li, D., & Zhang, B. (2019) · Clinical Science · doi:10.1042/cs20190715 · Cited by 83
Circular RNA HIPK3: A Key Circular RNA in a Variety of Human Cancers
Wen, J., Liao, J., Liang, J., Chen, X., Zhang, B., & Chu, L. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00773 · Cited by 86
“Exonic circRNAs (ecircRNAs), which make up 80% of identified circRNAs, are mainly derived from one or more exons (14, 17, 18).”
Background
PASSION: an ensemble neural network approach for identifying the binding sites of RBPs on circRNAs
Jia, C., Bi, Y., Chen, J.-X., Leier, A., Li, F., & Song, J. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa522 · Cited by 81
CircRNA-UBE2G1 regulates LPS-induced osteoarthritis through miR-373/HIF-1a axis
Chen, G., Liu, T., Yu, B., Wang, B., & Peng, Q. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1772545 · Cited by 83
“Circular RNAs (circRNAs) are a novel type of ncRNAs derived from exons, introns, or intergenic regions that have a covalently closed continuous loop, display cell or tissue specific expression, and are conserved across species due to resistance to RNase R [6,7].”
Background
Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer
Zhou, X., Liu, K., Cui, J., Xiong, J., Wu, H., Peng, T., & Guo, Y. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01894-x · Cited by 83
Long non-coding RNAs: a rising biotarget in colorectal cancer
Luo, J. G., Qu, J., Wu, D., Lu, Z., Sun, Y.-S., & Qu, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.14728 · Cited by 85
“reported that Ets-1 negatively regulates BANCR expression via the deacetylation of H3 histones within the BANCR promoter to influenced a fentanyl-induced mechanism, thereby inhibiting the invasion and migration of CRC cells [89].”
Background
CircRNA has_circ_0001946 promotes cell growth in lung adenocarcinoma by regulating miR-135a-5p/SIRT1 axis and activating Wnt/β-catenin signaling pathway
Yao, Y., Hua, Q., Zhou, Y., & Shen, H. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.12.120 · Cited by 82
Circular RNA DOCK1 promotes bladder carcinoma progression via modulating circDOCK1/hsa‐miR‐132‐3p/Sox5 signalling pathway
Liu, P., Li, X., Guo, X., Chen, J., Li, C., Chen, M., Liu, L., Zhang, X., & Zu, X. (2019) · Cell Proliferation · doi:10.1111/cpr.12614 · Cited by 83
CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA
Song, J., Wang, H., Song, K., Ding, Z., Wang, H., Ma, X., Lu, F., Xia, X., Wang, Y., Fei-Zou, et al. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0125-y · Cited by 81
Role of the ciRS-7/miR-7 axis in the regulation of proliferation, apoptosis and inflammation of chondrocytes induced by IL-1β.
Zhou, X.-D., Jiang, L.-F., Fan, G.-M., Yang, H.-Y., Wu, L.-D., Huang, Y., Xu, N.-W., & Li, J. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.037 · Cited by 71
Predicting CircRNA-Disease Associations Through Linear Neighborhood Label Propagation Method
Zhang, W., Yu, C., Wang, X., & Liu, F. (2019) · IEEE Access · doi:10.1109/access.2019.2920942 · Cited by 82
“CircRNAs play critical roles in biological processes including transcription, mRNA splicing [15], [16], RNA decay and translation [17].”
Background
RETRACTED: circIFT80 Functions as a ceRNA of miR-1236-3p to Promote Colorectal Cancer Progression
Feng, W., Gong, H., Wang, Y., Zhu, G., Xue, T., Wang, Y., & Cui, G. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.08.024 · Cited by 81
“A number of recent papers have revealed that circRNAs are highly dysregulated in many types of cancers and exhibit high tissue and disease specificity.(6,15) The deregulation of circRNAs may result in increased proliferation, invasion, or angiogenesis and decrease the level of apoptosis or dedifferentiation, eventuall…”
Background
Retracted
Circular RNA ITCH: A novel tumor suppressor in multiple cancers
Li, Y., Ge, Y., Xu, L., & Jia, R.-P. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.117176 · Cited by 81
hsa_circ_0026827 Promotes Osteoblast Differentiation of Human Dental Pulp Stem Cells Through the Beclin1 and RUNX1 Signaling Pathways by Sponging miR-188-3p
Ji, F., Zhu, L., Pan, J., Shen, Z., Yang, Z., Wang, J., Bai, X., Lin, Y., & Jiang, T. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00470 · Cited by 81
“In contrast to linear RNAs, circRNAs are constructed as a covalently closed continuous loops with their 5 tails and 3 heads bound together (Qu et al., 2015).”
Background
CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129
Zhang, Z., Zhu, H., & Hu, J. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03486-1 · Cited by 81
Circ100284, via miR-217 regulation of EZH2, is involved in the arsenite-accelerated cell cycle of human keratinocytes in carcinogenesis
Xue, J., Liu, Y., Luo, F., Lü, X., Xu, H., Liu, X., Lu, L., Yang, Q., Chen, C., Fan, W., et al. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.12.018 · Cited by 80
“circRNAs, a new type of endogenous noncoding RNAs, are expressed across various species, including flies andworms [39].”
Background

Authors: Qu, S., Yang, X., Li, X., Wang, J., Gao, Y., Shang, R., Sun, W., Dou, K., & Li, H.
Affiliations: Xijing Hospital (CN)
Corresponding author: Li, Haimin
ORCID: Qu, Shibin
Li, Xiaolei
Wang, Jianlin
Gao, Yuan
Shang, Runze
Sun, Wei
Dou, Kefeng
Li, Haimin
Venue: Cancer Letters
Publisher: Elsevier BV
Published: 2015-09
Volume: 365
Issue: 2
Pages: 141-148
ISSN: 0304-3835 (ISSN-L)
DOI: 10.1016/j.canlet.2015.06.003
OpenAlex: W1866220599
Cited by: 1,808
References: 71
Citations by year: 2026: 30 · 2025: 71 · 2024: 142 · 2023: 176 · 2022: 236 · 2021: 328 · 2020: 326 · 2019: 205 · 2018: 154 · 2017: 75 · 2016: 52 · 2015: 7
FWCI: 9.30
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cancer Letters (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81772061)
Health Public Welfare Industry Special Scientific Research Projects of China (201202007)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords: circular RNA, circRNA biogenesis, RNA-binding proteins, microRNA sponge, RNA splicing regulation, transcriptional regulation, circRNA stability, disease biomarkers, colorectal cancer, pancreatic ductal adenocarcinoma, atherosclerosis, neurological disorders, prion disease, long non-coding RNA
MeSH terms: RNA, Circular, Exoribonucleases, Gene Expression Regulation, Humans, Neoplasms, RNA, RNA Splicing, Transcription, Genetic, RNA, Untranslated

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Circular RNA: A new star of noncoding RNAs

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