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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“Circular RNAs (circRNAs), a novel class of noncoding RNAs characterized by covalently closed loop structures with neither 50 to 30 polarity nor a polyadenylated tail, are expressed in a tissue specific and stable manner.(10) CircRNAs are involved in various vascular diseases, including vascular dysfunction, carotid at…”
Background
mmu_circ_0000790 Is Involved in Pulmonary Vascular Remodeling in Mice with HPH via MicroRNA-374c-Mediated FOXC1
Yang, L., Liang, H., Meng, X., Shen, L., Guan, Z., Hei, B., Yu, H., Qi, S., & Wen, X. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.12.027 · Cited by 35
“Typically, several circRNAs play vital roles in diseases, particularly in different types of cancers, which, therefore, constitute novel potential targets for both the diagnosis and therapeutics for diseases.(13,14) Previous evidence has illustrated that overexpressed circRNAs are predominantly enriched in the ribonuc…”
Background
Circular RNAs: novel actors of Wnt signaling pathway in lung cancer progression
Alimohammadi, M., Gholinezhad, Y., Mousavi, V., Kahkesh, S., Rezaee, M., Yaghoobi, A., Mafi, A., & Araghi, M. (2023) · EXCLI journal · doi:10.17179/excli2023-6209 · Cited by 35
The circRNA interactome-innovative hallmarks of the intra- and extracellular radiation response
O’Leary, V. B., Smida, J., Matjanovski, M., Brockhaus, C., Winkler, K., Moertl, S., Ovsepian, S. V., & Atkinson, M. J. (2017) · Oncotarget · doi:10.18632/oncotarget.19228 · Cited by 35
“Comparative RNA-seq analysis of normal colon mucosa and colorectal tumours revealed circRNA reduction in malignant tissues [9], highlighting their potential as biomarkers or therapeutic targets [4, 10].”
Background
Unveiling ncRNA regulatory axes in atherosclerosis progression
Navarro, E., Mallén, A., Cruzado, J. M., Torrás, J., & Hueso, M. (2020) · Clinical and Translational Medicine · doi:10.1186/s40169-020-0256-3 · Cited by 35
circ-CBFB upregulates p66Shc to perturb mitochondrial dynamics in APAP-induced liver injury
Wang, Z., Zhao, Y., Sun, R., Sun, Y., Liu, D., Lin, M., Chen, Z., Zhou, J., Lv, L., Tian, X., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03160-y · Cited by 35
Non-coding RNAs in pancreatic ductal adenocarcinoma: New approaches for better diagnosis and therapy
Mortoglou, M., Tabin, Z. K., Arısan, E. D., Kocher, H. M., & Onganer, P. U. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101090 · Cited by 36
Non-coding RNAs in melanoma: Biological functions and potential clinical applications
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“circRNAs and melanoma In recent years, more and more studies have shown that circRNAs show strong functions in regulating cell proliferation, apoptosis, angiogenesis, and metastasis, indicating that circRNAs can be used as a cancer biomarker and may be an important therapeutic target for cancer.(155) Ju et al.”
Background
Molecular landscape of c-Myc signaling in prostate cancer: A roadmap to clinical translation
Faskhoudi, M. A., Molaei, P., Sadrkhanloo, M., Orouei, S., Hashemi, M., Bokaie, S., Rashidi, M., Entezari, M., Zarrabi, A., Hushmandi, K., et al. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153851 · Cited by 40
Epigenetic Regulation of Ferroptosis in Central Nervous System Diseases
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“Unlike linear RNA, circRNA forms a closed circular structure, making it hard to cut by RNA exonuclease [45].”
Background
Long noncoding RNA/circular RNA regulates competitive endogenous RNA networks in rheumatoid arthritis: molecular mechanisms and traditional Chinese medicine therapeutic significances
Wen, J., Liu, J., Wan, L., & Wang, F. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2172605 · Cited by 37
“But, it is important to note that circRNA is conserved and stable, and formed through back-splicing events of precursor mRNA, which should avoid recognition of their cognate linear RNAs [109].”
Background
Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration
Kunze, R., Fischer, S., Marti, H. H., & Preissner, K. T. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00954-y · Cited by 37
“Thus, circRNAs are considered as post-transcriptional regulatory elements [313].”
Background
Role of genomic DNA methylation in PCOS pathogenesis: a systematic review and meta-analysis involving case-controlled clinical studies
Rawat, K., Sandhu, A., Gautam, V., Saha, P. K., & Saha, L. (2022) · Molecular Human Reproduction · doi:10.1093/molehr/gaac024 · Cited by 34
The role and regulation of Maf proteins in cancer
Deng, Y., Lu, L., Zhang, H., Fu, Y., Liu, T., & Chen, Y. (2023) · Biomarker Research · doi:10.1186/s40364-023-00457-w · Cited by 36
“There are several major types of ncRNAs: small RNAs including miRNAs [67], circular RNAs (circRNAs) [68] and long noncoding RNAs (lncRNAs) [69] et al.”
Background
A computationally constructed ceRNA interaction network based on a comparison of the SHEE and SHEEC cell lines
Sun, J., Yan, J.-Q., Yuan, X.-Z., Yang, R., Dan, T.-Y., Wang, X.-S., Kong, G.-Q., & Gao, S.-G. (2016) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-016-0022-0 · Cited by 34
“Some studies have confirmed that ceRNAs play an important role in the regulation of gene expression in cancers such as head and neck squamous cell carcinoma, prostate cancer, papillary thyroid carcinoma, pituitary gonadotrope tumors, ovarian cancer, and chronic lymphocytic leukemia [44 – 46].”
Background
Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis
Xu, X., Jia, S., Dai, Y., Zhang, J., Li, X., Shi, J., Leng, J., & Lang, J. (2018) · Chinese Medical Journal · doi:10.4103/0366-6999.226070 · Cited by 34
“[6‐8] Moreover, circRNAs are characterized by covalently linked terminals and high stability as well as abundant expression level.[9,10] All abovementioned characteristics make circRNAs become evaluate indicators for diagnosis, prognosis, and therapeutic‐response prediction.”
Background
Upregulation of circ_001569 predicts poor prognosis and promotes cell proliferation in non‑small cell lung cancer by regulating the Wnt/β‑catenin pathway
Ding, L., Yao, W., Lu, J., Gong, J., & Zhang, X. (2018) · Oncology Letters · doi:10.3892/ol.2018.8673 · Cited by 34
Viroid research and its significance for RNA technology and basic biochemistry
Steger, G., & Riesner, D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky903 · Cited by 34
“CircRNAs are now recognized as a large class of RNA which are non-coding and non-infectious, have a prolonged half-life, function in the regulation of gene expression or are of unknown function (15,16).”
Background
Characterization of Circular RNAs in Chinese Buffalo (Bubalus bubalis) Adipose Tissue: A Focus on Circular RNAs Involved in Fat Deposition
Huang, J., Zhao, J., Zheng, Q., Wang, S., Wei, X., Li, F., Shang, J., Lei, C., & Ma, Y. (2019) · Animals · doi:10.3390/ani9070403 · Cited by 33
“Previous studies have indicated that circRNAs can regulate the expression of their host genes [7,37,40].”
Background
RETRACTED: Silencing circular RNA VANGL1 inhibits progression of bladder cancer by regulating miR‐1184/IGFBP2 axis
Yang, D., Qian, H., Fang, Z. Y., Xu, A. T., Zhao, S., Liu, B., & Dong, L. (2019) · Cancer Medicine · doi:10.1002/cam4.2650 · Cited by 34
Retracted
Changed cellular functions and aberrantly expressed miRNAs and circRNAs in bone marrow stem�cells in osteonecrosis of the femoral head
Xiang, S., Zeng, L., & Weng, X. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4455 · Cited by 34
“circRNAs could bind miRNAs and function through a ceRNA mechanism (29).”
CircRNA Expression Profile during Yak Adipocyte Differentiation and Screen Potential circRNAs for Adipocyte Differentiation
Zhang, Y., Guo, X., Pei, J., Chu, M., Ding, X., Wu, X., Liang, C., & Yan, P. (2020) · Genes · doi:10.3390/genes11040414 · Cited by 34
“It is a class of RNAs that form covalently bounded closed-loop structures having neither 5’ to 3’ polarities nor polyadenylated tails [4] and exist abundantly in eukaryotes [5].”
Background
CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182
Jia, Y., Liu, M., & Wang, S. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01437-y · Cited by 34
Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells
Kang, L., Hao, J., Huang, B., Lu, S., Chen, Z., Shen, J., Zou, Y., Wang, C., & Sun, Y. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.596169 · Cited by 34
CircRNA Microarray Profiling Reveals hsa_circ_0058493 as a Novel Biomarker for Imatinib-Resistant CML
Zhong, A.-N., Yin, Y., Tang, B.-J., Chen, L., Shen, H., Tan, Z., Li, W., He, Q., Sun, B., Zhu, Y. M., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.728916 · Cited by 34
“CircRNAs are a special novel type of endogenous noncoding RNA with covalently closed-loop structures, which makes them much more stable than liner RNA (Qu et al., 2015).”
Background
Serum and Serum Exosomal CircRNAs hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 as Diagnostic Biomarkers for Lung Adenocarcinoma
Kang, Y., You, J., Gan, Y., Chen, Q., Huang, C., Chen, F., Xu, X., & Chen, L. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.912246 · Cited by 34
Practical Significance of Biomarkers in Axial Spondyloarthritis: Updates on Diagnosis, Disease Activity, and Prognosis
Diaconu, A.-D., Ceasovschih, A., Șorodoc, V., Pomîrleanu, C., Lionte, C., Șorodoc, L., & Ancuța, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911561 · Cited by 36
Multi-omics approaches for biomarker discovery and precision diagnosis of prediabetes
Song, J., Wang, C., Zhao, T., Zhang, Y., Xing, J., Zhao, X., Zhang, Y., & Zhang, Z. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1520436 · Cited by 36
Circular RNA expression profile analysis of severe acne by RNA ‐Seq and bioinformatics
Liang, J., Wu, X., Sun, S., Chen, P., Liang, X., Wang, J., Ruan, J., Zhang, S., & Zhang, X. (2018) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.14948 · Cited by 33
Preliminary investigation of the function of hsa_circ_0006215 in pancreatic cancer
Zhu, P., Ge, N., Liu, D., Yang, F., Zhang, K., Guo, J., Liu, X., Wang, S., Wang, G., & Sun, S. (2018) · Oncology Letters · doi:10.3892/ol.2018.8652 · Cited by 33
“CircRNAs are a class of specific endogenous RNAs, and are characterized by stable structure and increased tissue‑specific expression (14).”
The modular organization of the cerebral cortex: Evolutionary significance and possible links to neurodevelopmental conditions
Casanova, M. F., & Casanova, M. (2018) · The Journal of Comparative Neurology · doi:10.1002/cne.24554 · Cited by 37
“• Circular RNA (circRNA), which function as “microRNA sponges” (Qu et al., 2015).”
Background
Characterization of circRNA‑associated ceRNA networks in patients with nonvalvular persistent atrial fibrillation
Zhang, Y., Ke, X., Liu, J., Ma, X., Liu, Y., Liang, D., Wang, L., Guo, C., & Luo, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9695 · Cited by 32
“Unlike linear RNAs, circRNAs are covalently linked to form closed-loop structures without 5' caps or 3' tails (18,23 -25).”
A comprehensive profile of the tilapia ( Oreochromis niloticus ) circular RNA and circRNA–miRNA network in the pathogenesis of meningoencephalitis of teleosts
Fan, B., Chen, F., Li, Y., Wang, Z., Wang, Z., Lu, Y., Wu, Z., Jian, J., & Wang, B. (2019) · Molecular Omics · doi:10.1039/c9mo00025a · Cited by 33
The roles of circRFWD2 and circINO80 during NELL‐1‐induced osteogenesis
Huang, X., Cen, X. B., Zhang, B., Liao, Y., Zhao, Z., Zhu, G., Zhao, Z., & Liu, J. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14726 · Cited by 33
Down-regulation of miR-30b-5p protects cardiomyocytes against hypoxia-induced injury by targeting Aven
Zhang, L.-F., & Jia, X. (2019) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-019-0187-4 · Cited by 23
CircRNA_101951 promotes migration and invasion of colorectal cancer cells by regulating the KIF3A‑mediated EMT pathway
Li, Y., Pei, F., & Cao, M. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8600 · Cited by 33
“Circular RNAs (circRNAs), which are covalent closed loops of RNA (5-7), are reported to serve vital roles in the proliferation and metastasis of tumors (8-12).”
Background
hsa_circ_0072387 Suppresses Proliferation, Metastasis, and Glycolysis of Oral Squamous Cell Carcinoma Cells by Downregulating miR-503-5p
Han, L., Cheng, J., & Li, A. (2020) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2019.3371 · Cited by 33
Circular RNA expression profiling reveals that circ-PLXNA1 functions in duck adipocyte differentiation
Wang, L., Liang, W., Wang, S., Wang, Z., Bai, H., Jiang, Y., Bi, Y., Chen, G., & Chang, G. (2020) · PLoS ONE · doi:10.1371/journal.pone.0236069 · Cited by 33
“CircRNAs are a novel class of endogenous non-coding RNAs characterized by a stable and covalently closed loop [7,8].”
Circular RNA Hsa_circ_0004018 Inhibits Wnt/β-Catenin Signaling Pathway by Targeting microRNA-626/DKK3 in Hepatocellular Carcinoma
Zhu, P., Liang, H., Huang, X., Qinglei, Z., Liu, Y., Lv, J., & Ming, L. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s254997 · Cited by 33
Circ_0000079 Decoys the RNA-Binding Protein FXR1 to Interrupt Formation of the FXR1/PRCKI Complex and Decline Their Mediated Cell Invasion and Drug Resistance in NSCLC
Chen, C., Zhang, M., & Zhang, Y. (2020) · Cell Transplantation · doi:10.1177/0963689720961070 · Cited by 33
Circ_0001944 Contributes to Glycolysis and Tumor Growth by Upregulating NFAT5 Through Acting as a Decoy for miR-142-5p in Non-Small Cell Lung Cancer
Dou, Y., Tian, W., Wang, H., & Lv, S. (2021) · Cancer Management and Research · doi:10.2147/cmar.s302814 · Cited by 33
CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma
Wang, X., Dong, J., Li, X., Cheng, Z., & Zhu, Q. (2021) · Oncogene · doi:10.1038/s41388-021-01867-6 · Cited by 33
“various snRNAs and protein components [18].”
Circular RNA circACSL1 aggravated myocardial inflammation and myocardial injury by sponging miR-8055 and regulating MAPK14 expression
Zhang, L., Han, B., Liu, H., Wang, J., Feng, X., Sun, W., Cai, D., Jia, H., & Jiang, D. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03777-7 · Cited by 33
Hsa_circ_0066523 promotes the proliferation and osteogenic differentiation of bone mesenchymal stem cells by repressing PTEN
Xin, W., Yuan, S., Wang, B., Qian, Q., & Chen, Y. (2021) · Bone and Joint Research · doi:10.1302/2046-3758.108.bjr-2020-0127.r2 · Cited by 33
CircRNA FAT1 Regulates Osteoblastic Differentiation of Periodontal Ligament Stem Cells via miR-4781-3p/SMAD5 Pathway
Ye, Y., Ke, Y., Liu, L., Tong, X., & Yu, J. (2021) · Stem Cells International · doi:10.1155/2021/5177488 · Cited by 33
“CircRNAs have been applied in clinical treatment or disease diagnosis as biomarkers or targets [18].”
Method
HCRNet: high-throughput circRNA-binding event identification from CLIP-seq data using deep temporal convolutional network
Yang, Y., Hou, Z., Wang, Y., Ma, H., Sun, P., Ma, Z., Wong, K., & Li, X. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac027 · Cited by 35
CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90β complex
Chen, K., Chen, X., Lang, C., Yuan, X., Huang, J., Li, Z., Xu, M., Wu, K., Zhou, C., Li, Q., et al. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01085-y · Cited by 32
Mechanistic insights into circRNA-mediated regulation of PI3K signaling pathway in glioma progression
Mafi, A., Khoshnazar, S. M., Shahpar, A., Nabavi, N., Hedayati, N., Alimohammadi, M., Hashemi, M., Taheriazam, A., & Farahani, N. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155442 · Cited by 33
Non‐coding RNAs in cardiac hypertrophy
Ottaviani, L., & Martins, P. A. D. C. (2017) · The Journal of Physiology · doi:10.1113/jp273129 · Cited by 33
“It is assumed that circRNAs do not code for proteins due to their circular structure and, in contrast to other non-coding RNAs, the lack of both 5′ and 3′ polarity and a poli-A tail (Qu et al. 2015; Chen, 2016).”
BackgroundInfluential
Circular RNAs in Cardiovascular Diseases
Wang, L., Meng, X., Li, G., Zhou, Q., & Xiao, J. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1426-1_15 · Cited by 32
Circular RNAs Serve as Novel Biomarkers and Therapeutic Targets in Cancers
Fang, S., Pan, J., Zhou, C., Tian, H., He, J., Shen, W., Jin, X., Meng, X., Jiang, N., & Gong, Z. (2018) · Current Gene Therapy · doi:10.2174/1566523218666181109142756 · Cited by 32
Microarray expression profile of circular RNAs and mRNAs in children with systemic lupus erythematosus
Li, S., Zhang, J., Tan, X., Deng, J., Li, Y., Piao, Y., Li, C., Yang, W., Mo, W., Sun, F., et al. (2019) · Clinical Rheumatology · doi:10.1007/s10067-018-4392-8 · Cited by 32
Circular RNA expression in pancreatic ductal adenocarcinoma
Zhang, Q., Wang, J., Zhou, S., Yang, S., & Zhong, S. (2019) · Oncology Letters · doi:10.3892/ol.2019.10624 · Cited by 32
“Previous studies have shown that circRNAs modulate the expression of their parental genes (6,7,28,29).”
BackgroundInfluential
hsa_circ_0062389 promotes the progression of non-small cell lung cancer by sponging miR-103a-3p to mediate CCNE1 expression
She, Y., Han, Y., Zhou, G., Jia, F., Yang, T., & Shen, Z. (2019) · Cancer Genetics · doi:10.1016/j.cancergen.2019.12.004 · Cited by 32
Expression profile and bioinformatics analyses of circular RNAs in keloid and normal dermal fibroblasts
Zhang, Z., Yu, K., Liu, O., Xiong, Y., Yang, X., Wang, S., Zhang, S., Feng, Y., & Peng, Y. (2020) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.111799 · Cited by 32
Circular RNA hsa_circ_0000848 Promotes Trophoblast Cell Migration and Invasion and Inhibits Cell Apoptosis by Sponging hsa-miR-6768-5p
Wang, H., Zhang, J., Xu, Z., Yang, J., Xu, Y., Liu, Y., Li, B., Xie, J., & Li, J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00278 · Cited by 31
Circular RNA UBAP2 contributes to tumor growth and metastasis of cervical cancer via modulating miR-361-3p/SOX4 axis
Meng, L., Jia, X., Yu, W., Wang, C., Chen, J., & Liu, F. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01436-z · Cited by 32
“Discussion CircRNAs are naturally occurring, versatile and diverse endogenous non-coding RNAs, and have covalently linked ends relative to linear RNAs [23, 24].”
Background
Upregulated circPDK1 Promotes RCC Cell Migration and Invasion by Regulating the miR-377-3P-NOTCH1 Axis in Renal Cell Carcinoma
Huang, Z., Ding, Y., Zhang, L., He, S., Jia, Z., Gu, C., Wang, T., Li, H., Li, X., Jin, Z., et al. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s280434 · Cited by 32
Biogenesis and functions of circular RNAs and their role in diseases of the female reproductive system
Ma, Y., Xu, Y., Zhang, J., & Zheng, L. (2020) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-020-00653-5 · Cited by 33
“In addition to miRNA regulation, circRNAs can regulate the intracellular transport of RNA-binding proteins (RBPs) [8, 9].”
Background
Identification and Characterization of circRNA in Longissimus Dorsi of Different Breeds of Cattle
Liu, R., Liu, X., Bai, X., Xiao, C., & Dong, Y. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.565085 · Cited by 30
“circRNA can be obtained by transcription of protein-coding genes or intergenic regions (Qu et al., 2015).”
Background
The Roles of CircRNAs in Regulating Muscle Development of Livestock Animals
Yang, Z., He, T., & Chen, Q. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.619329 · Cited by 33
LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis
Ge, J., Yan, D., Ge, C., & Wei, M. (2020) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v12.i11.1272 · Cited by 31
Enhancer RNA (eRNA) in Human Diseases
Wang, Y., Zhang, C., Wang, Y., Liu, X., & Zhang, Z. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911582 · Cited by 33
“Overall, regulatory ncRNAs are involved in miscellaneous biological processes, varying from cell proliferation to pluripotency, showing a big potential in understanding and diagnosing cancers, inflammation responses and other diseases [17,35].”
Background
Identification of circular RNA signature in bladder cancer
Yang, X. F., Yuan, W., Tao, J., Li, P., Yang, C., Deng, X., Zhang, X., Tang, J., Han, J., Wang, J., et al. (2017) · Journal of Cancer · doi:10.7150/jca.19345 · Cited by 31
“Recently, the role of circRNA in tumourigenesis has been demosntrated [22,23].”
Background
Circular RNA hsa-circ-0012129 Promotes Cell Proliferation and Invasion in 30 Cases of Human Glioma and Human Glioma Cell Lines U373, A172, and SHG44, by Targeting MicroRNA-661 (miR-661)
., G. X. (2018) · Medical Science Monitor · doi:10.12659/msm.909229 · Cited by 31
“Circular RNA (circRNA) is an endogenous non-coding RNA that is produced in the process of RNA shearing [12].”
Background
Differential Expression Profiles of Circular RNAs During Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells
Long, T., Guo, Z., Han, L., Yuan, X., Liu, L., Jing, W., Tian, W., Zheng, X., Tang, W. D., & Long, J. (2018) · Calcified Tissue International · doi:10.1007/s00223-018-0426-0 · Cited by 30
Systematic investigation of circular RNAs in Ascosphaera apis, a fungal pathogen of honeybee larvae
Guo, R., Chen, D., Chen, H., Fu, Z., Xiong, C., Hou, C., Zheng, Y., Guo, Y., Wang, H., Du, Y., et al. (2018) · Gene · doi:10.1016/j.gene.2018.07.076 · Cited by 31
The progress of circular RNAs in various tumors.
Wang, D., Yang, S., Wang, H., Wang, J., Zhang, Q., Zhou, S., He, Y., Zhang, H., Deng, F., Xu, H., et al. (2018) · Europe PMC (PubMed Central) · Cited by 31
Hsa_Circ_0007841 Enhances Multiple Myeloma Chemotherapy Resistance Through Upregulating ABCG2
Song, Y. Y., Hu, N., Song, X., & Yang, J. (2020) · Technology in Cancer Research & Treatment · doi:10.1177/1533033820928371 · Cited by 31
“One the most reported function of circRNAs is acting as endogenous miRNA sponges since some circRNAs have microRNA-binding sites allowing them to arrest microRNA.(8,9) Abundance and relative stable structure make circRNAs to be effective sponges than linear messenger RNAs (mRNAs).”
Background
Novel circRNA_0071196/miRNA‑19b‑3p/CIT axis is associated with proliferation and migration of bladder cancer
Liu, Z., Yang, Y., Yang, Z., Xia, S., Lin, D., Xiao, B., & Xiu, Y. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5093 · Cited by 31
“CircRNAs are a class of covalently closed endogenous ncRNAs (9) that are differentially expressed in various types of cancers, such as liver carcinoma, stomach carcinoma and colorectal carcinoma, and correlated with tumor development and progression (10,11).”
RETRACTED ARTICLE: Circular RNA hsa_circ_0000517 modulates hepatocellular carcinoma advancement via the miR-326/SMAD6 axis
He, S., Guo, Z., Kang, Q., Wang, X., & Han, X. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01447-w · Cited by 31
Retracted
The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers
Limb, C., Liu, D., Venø, M. T., Rees, E., Krell, J., Bagwan, I., Giovannetti, E., Pandha, H., Strobel, O., Rockall, T., et al. (2020) · Cancers · doi:10.3390/cancers12113250 · Cited by 31
Genomic analysis of circular RNAs in heart
Dong, K., He, X., Su, H., Fulton, D. J., & Zhou, J. (2020) · BMC Medical Genomics · doi:10.1186/s12920-020-00817-7 · Cited by 31
Circular RNA in tumor metastasis
Zhang, C., Ding, R., Sun, Y., Huo, S. T., He, A. T., Wen, C., Chen, H., Du, W. W., Lai, W., & Wang, H. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.01.032 · Cited by 31
“Despite the relatively low efficiency of back-splicing compared to forward-splicing of linear RNAs, there is still an abundance of circRNAs because of their stability and longer half-life.(61)”
Background
Identification of Circulating hsa_circ_0063425 and hsa_circ_0056891 as Novel Biomarkers for Detection of Type 2 Diabetes
Lu, Y., Chu, X., Wang, S., Sun, Y., Zhang, J., Dong, J., & Yan, Y. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab101 · Cited by 31
The Role of N6-Methyladenosine Modified Circular RNA in Pathophysiological Processes
Tang, M., & Lv, Y. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.60131 · Cited by 32
“Artificial circRNAs with a RES can be translated in vitro or in vivo [79-81].”
Background
Knockdown of circ‑PVT1 inhibits the progression of lung adenocarcinoma and enhances the sensitivity to cisplatin via the miR‑429/FOXK1 signaling axis
Cao, L., Zhou, X., Ding, X., & Gao, D. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12323 · Cited by 31
Circular RNA circUSP13 sponges miR‐29c to promote differentiation and inhibit apoptosis of goat myoblasts by targeting IGF1
Zhang, Z., Fan, Y., Deng, K., Liang, Y., Zhang, G., Gao, X., El-Samahy, M. A., Zhang, Y., Deng, M., & Wang, F. (2021) · The FASEB Journal · doi:10.1096/fj.202101317r · Cited by 31
Cancer stem cell-specific expression profiles reveal emerging bladder cancer biomarkers and identify circRNA_103809 as an important regulator in bladder cancer
Tao, T., Yuan, S., Liu, J., Shi, D., Peng, M., Li, C., & Wu, S. (2020) · Aging · doi:10.18632/aging.102816 · Cited by 31
“Two types of RNA without protein-coding potentials, termed as long non-coding RNA (lncRNA) and circular RNA (circRNA), were identified [8, 9] and proved to play important roles in many diseases recently [10–12].”
Background
CircMIB2 therapy can effectively treat pathogenic infection by encoding a novel protein
Zheng, W., Wang, L., Geng, S., Yang, L., Lv, X., Xin, S., & Xu, T. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06105-3 · Cited by 31
“Epithelioma papulosum cyprini cells (EPC) were maintained in medium 199 medium (Invitrogen) supplemented with 10% FBS, 100 U/ml penicillin, and 100 mg/ ml streptomycin at 28 °C in 5% CO 2 [26].”
Overexpression of circ‑0067934 is associated with increased cellular proliferation and the prognosis of non‑small cell lung cancer
Zou, Q., Wang, T., Li, B., Guanghu, L., Zhang, L., Wang, B., & Sun, S. (2018) · Oncology Letters · doi:10.3892/ol.2018.9357 · Cited by 30
Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR‐488‐3p in Hirschsprung's disease
Wen, Z., Shen, Q., Zhang, H., Su, Y., Zhu, Z., Chen, G., Peng, L., Li, H., Du, C., Xie, H., et al. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27733 · Cited by 30
“Additionally, RNase R enzyme was applied, which only acts on linear RNAs but not circRNAs (Hossain, Malhotra, & Deutscher, 2016; Qu et al., 2015).”
Method
Predicting circRNA–Disease Associations Based on Improved Collaboration Filtering Recommendation System With Multiple Data
Lei, X., Fang, Z., & Guo, L. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00897 · Cited by 31
“Many recent evidences (Danan et al., 2011) show that circRNAs play significant roles in different biological processes and have multiple biological functions (Jeck and Sharpless, 2014; Qu et al., 2015).”
Background
Identification of hsa_circ_0001821 as a Novel Diagnostic Biomarker in Gastric Cancer via Comprehensive Circular RNA Profiling
Kong, S., Yang, Q., Tang, C., Wang, T., Shen, X., & Ju, S. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00878 · Cited by 30
“Differentially expressed genes were identified using the edgeR program (Robinson et al., 2010).”
Method
RETRACTED ARTICLE: Circ_0002770, acting as a competitive endogenous RNA, promotes proliferation and invasion by targeting miR-331-3p in melanoma
Qian, P., Linbo, L., Xiaomei, Z., & Hui, P. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2444-x · Cited by 30
Retracted
Circular RNA Expression Profiles in Nasopharyngeal Carcinoma by Sequence Analysis
Yang, J., Gong, Y., Jiang, Q., Liu, L., Li, S., Zhou, Q., Huang, F., & Liu, Z. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00601 · Cited by 30
RETRACTED: Circ_0085296 suppresses trophoblast cell proliferation, invasion, and migration via modulating miR-144/E-cadherin axis
Zhu, H., Niu, X., Li, Q., Zhao, Y., Chen, X., & Sun, H. (2020) · Placenta · doi:10.1016/j.placenta.2020.06.002 · Cited by 30
Retracted
CircZNF609 promotes cell proliferation, migration, invasion, and glycolysis in nasopharyngeal carcinoma through regulating HRAS via miR-338-3p
Liu, Z., Liu, F., Wang, F., Yang, X., & Guo, W. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03894-5 · Cited by 31
Expression and clinical significance of circular RNAs related to immunity and inflammation in patients with rheumatoid arthritis
Wen, J., Liu, J., Wang, X., & Wang, J. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107366 · Cited by 30
Hsa_circ_0107593 Suppresses the Progression of Cervical Cancer via Sponging hsa-miR-20a-5p/93-5p/106b-5p
Liao, W., He, J., Disoma, C., Hu, Y., Li, J., Chen, G., Sheng, Y., Cai, X., Li, C., Cheng, K., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.590627 · Cited by 30
“CircRNAs have recently emerged as a new class of endogenous RNAs that are formed by a covalently closed continuous loop without 5′ caps and 3′ tails compared to mRNAs, and exist extensively in mammalian cells (16, 17).”
Background
circRNA_0005529 facilitates growth and metastasis of gastric cancer via regulating miR-527/Sp1 axis
Zhang, X., Yang, H., Jia, Y., Xu, Z., Zhang, L., Sun, M., & Fu, J. (2021) · BMC Molecular and Cell Biology · doi:10.1186/s12860-020-00340-8 · Cited by 30
“processes, including microRNA (miRNA) interaction, protein binding and regulative splicing [7, 8].”
Background
Genome‐wide profiling of circular RNAs, alternative splicing, and R‐loops in stem‐differentiating xylem of Populus trichocarpa
Liu, X., Gao, Y., Liao, J., Miao, M., Chen, K., Xi, F., Wei, W., Wang, H., Wang, Y., Xu, X., et al. (2021) · Journal of Integrative Plant Biology · doi:10.1111/jipb.13081 · Cited by 30
Sp1-Mediated circRNA circHipk2 Regulates Myogenesis by Targeting Ribosomal Protein Rpl7
Yan, J., Yang, Y., Fan, X., Tang, Y., & Tang, Z. (2021) · Genes · doi:10.3390/genes12050696 · Cited by 31
“The aberrant expression of circRNAs is also reported to be associated with muscular disease [7,12,13].”
Background
Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis
Huang, Y., Zheng, S., Lin, Y. N., & Ke, L. (2021) · Molecular and Cellular Biology · doi:10.1128/mcb.00609-20 · Cited by 30
“cial structure, most circRNAs are stable and resistant to RNase R (14).”
Background
Circular RNA circ‐FIRRE interacts with HNRNPC to promote esophageal squamous cell carcinoma progression by stabilizing GLI2 mRNA
Zhou, Y., Xue, X., Luo, J., Li, P., Xiao, Z., Zhang, W., Zhou, J., Li, P., Zhao, J., Ge, H., et al. (2023) · Cancer Science · doi:10.1111/cas.15899 · Cited by 31
Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma
Li, L., & Zhang, Z. (2020) · Medical Science Monitor · doi:10.12659/msm.919383 · Cited by 30
Computational approaches for circRNAs prediction andin silicocharacterization
Rebolledo, C., Silva, J. P., Saavedra, N., & Maracaja‐Coutinho, V. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad154 · Cited by 30
“In cancer, circSMARCA5 has been correlated with tumor differentiation and cancer diameter [19], whereas circCDYL has been shown to act as a predictive and prognostic marker of breast cancer [20].”
Background
Synthesis and Engineering of Circular RNAs
Petkovic, S., & Müller, S. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7562-4_14 · Cited by 29
Comprehensive analysis of microarray expression profiles of circRNAs and lncRNAs with associated co-expression networks in human colorectal cancer
Tian, Y., Xu, Y., Wang, H., Shu, R., Sun, L. D., Zeng, Y., Gong, F., Lei, Y., Wang, K., & Luo, H. (2018) · Functional & Integrative Genomics · doi:10.1007/s10142-018-0641-9 · Cited by 29
CircPRKCI-miR-545/589-E2F7 axis dysregulation mediates hydrogen peroxide-induced neuronal cell injury
Cheng, Q., Cao, X., Xue, L., Xia, L., & Xu, Y. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.04.131 · Cited by 29

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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