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
Retracted
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Non-coding RNAs: the new central dogma of cancer biology
Saw, P. E., Xu, X., Chen, J., & Song, E. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1700-9 · Cited by 180
“…(Bachmayr-Heyda et al., 2015), and when normal tissues were compared with those of colorectal and ovarian cancers, were globally reduced in cancer cell lines and cancer tissues. circRNAs function mostly by sponging miRNAs, which in turn could influence gene expression (Qu et al., 2015).”
BackgroundInfluential
A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
Peng, Y., Xu, Y., Zhang, X., Deng, S., Yuan, Y., Luo, X., Hossain, M. T., Zhu, X., Du, K., Hu, F., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01457-w · Cited by 175
“CircRNAs are expressed in a tissue-specific, developmental stage-specific, and diseasespecific manner [4].”
Background
A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548g in the cytoplasm and interacting with YBX1 in the nucleus
Fang, J. C., Hong, H., Xue, X., Zhu, X., Jiang, L., Qin, M., Liang, H., & Gao, L. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.10.040 · Cited by 169
CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis
Jin, X., Feng, C.-Y., Xiang, Z., Chen, Y., & Li, Y. (2016) · Oncotarget · doi:10.18632/oncotarget.12186 · Cited by 166
Circular RNA hsa_circ_0001982 Promotes Breast Cancer Cell Carcinogenesis Through Decreasing miR-143
Tang, Y., Zhao, P., Zou, T., Duan, J.-J., Zhi, R., Yang, S., Yang, D., & Wang, X. (2017) · DNA and Cell Biology · doi:10.1089/dna.2017.3862 · Cited by 164
“CircularRNAs (circRNAs) are type of RNAs characterized by covalent closed loops formed by back-splicing (Qu et al. , 2015).”
Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication
Klinge, C. M. (2018) · Non-Coding RNA · doi:10.3390/ncrna4040040 · Cited by 166
“circRNAs can act as competing endogenous RNA (ceRNA, also called ‘sponge’) for microRNAs, thus reducing miRNA repression of their target mRNAs [75].”
Background
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
Chen, J., Liu, G., Wu, Y., Ma, J., Wu, H.-F., Xie, Z., Chen, S., Yang, Y., Wang, S., Shen, P., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1076-1 · Cited by 164
“CircRNA is a class of single-stranded ncRNA derived from exons, introns, or intergenic regions of genes by back-splicing [10, 11].”
Background
The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p
Chen, D., Sheng, H., Zhang, D., Jin, Y., Zhao, B.-T., Chen, N., Song, K., & Xu, R. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01475-8 · Cited by 162
“Circular RNAs (circRNAs) are a class of recently identified noncoding RNAs or protein-coding RNAs that are characterized by covalently closed loops without 5′ to 3′ polarity or polyadenylation (polyA) tails [16].”
Background
Circular RNA Expression Profile of Pancreatic Ductal Adenocarcinoma Revealed by Microarray
Li, H., Hao, X., Wang, H., Liu, Z., He, Y., Pu, M., Zhang, H., Yu, H., Duan, J., & Qu, S. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000453186 · Cited by 155
Prediction of CircRNA-Disease Associations Using KATZ Model Based on Heterogeneous Networks
Fan, C., Lei, X., & Wu, F. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.28260 · Cited by 155
“In addition, circRNAs can regulate gene expression at transcriptional or post-transcriptional levels by titrating microRNAs (miRNAs), regulating transcription and interfering with splicing [13, 14].”
Background
Mini Review: Circular RNAs as Potential Clinical Biomarkers for Disorders in the Central Nervous System
Lu, D., & Xu, A.-D. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00053 · Cited by 154
“These circRNAs are more stable than linear-RNAs, indicating circRNAs themselves could serve as biomarkers of CNS disorders (Qu et al., 2015).”
Comprehensive profile of differentially expressed circular RNAs reveals that hsa_circ_0000069 is upregulated and promotes cell proliferation, migration, and invasion in colorectal cancer
Guo, J., Li, J., Zhu, C., Feng, W.-T., Shao, J.-X., Wan, L., Huang, M., & He, J. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s123220 · Cited by 153
“Emerging evidence has revealed that circRNAs can serve as microRNA sponges, RNA-binding proteins or transcriptional regulators to participate in the initiation and development of multiple diseases, such as Alzheimer’s disease, Parkinson’s disease, atherosclerosis, and cancers.(4,5) Several circRNAs have already been f…”
Background
Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis
Wang, H., Xiao, Y., Wu, L., & Ma, D. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4265 · Cited by 151
“Emerging evidence indicates that some circRNAs act as miRNA sponges to modulate gene transcription and interact with RNA-binding proteins (RBPs) involved in tumorigenesis (13,14).”
CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression
Zhang, D., Ni, N., Wang, Y., Tang, Z., Gao, H., Ju, Y., Sun, N., He, X., Gu, P., & Fan, X. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0600-6 · Cited by 149
“Concerning the mechanisms of action for circRNAs, one mode reported was the microRNAs (miRNAs) “sponges” activity of some exonic circRNAs [16].”
Background
hsa_circRNA_0006528 as a competing endogenous RNA promotes human breast cancer progression by sponging miR‐7‐5p and activating the MAPK/ERK signaling pathway
Gao, D., Qi, X., Zhang, X., Fang, K., Guo, Z., & Li, L. (2018) · Molecular Carcinogenesis · doi:10.1002/mc.22950 · Cited by 147
CircRNAs in hematopoiesis and hematological malignancies
Bonizzato, A., Gaffo, E., Kronnie, G. T., & Bortoluzzi, S. (2016) · Blood Cancer Journal · doi:10.1038/bcj.2016.81 · Cited by 147
Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients
Ouyang, Q., Wu, J., Jiang, Z., Zhao, J., Wang, R., Lou, A., Zhu, D., Shi, G., & Yang, M. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477883 · Cited by 146
CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway
Wang, M., Chen, B., Ru, Z., & Li, C. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.08.175 · Cited by 147
Non-coding RNAs as liquid biopsy biomarkers in cancer
Toden, S., & Goel, A. (2022) · British Journal of Cancer · doi:10.1038/s41416-021-01672-8 · Cited by 156
Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma
Xiao‐Long, M., Zhu, K., & Zhang, C. (2018) · Journal of Cancer · doi:10.7150/jca.24619 · Cited by 144
“Circular RNA (circRNA) is a new class of endogenously expressed non-coding RNA, which is characterized by covalently closed loop structures with neither 5’ to 3’ polarity nor polyadenylated tail[4].”
Background
Circular RNA hsa_circRNA_103809 promotes lung cancer progression via facilitating ZNF121-dependent MYC expression by sequestering miR-4302
Liu, W., Ma, W., Yuan, Y., Zhang, Y., & Sun, S. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.04.172 · Cited by 143
Circular RNA hsa_circ_0001564 regulates osteosarcoma proliferation and apoptosis by acting miRNA sponge
Song, Y.-Z., & Li, J. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.12.050 · Cited by 139
CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain
Zhang, S., Lin, S., Liu, M., Liu, C.-C., Ding, H., Sun, Y., Ma, C., Guo, R., Lv, Y., Wu, S.-L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12049-0 · Cited by 142
Predicting disease-associated circular RNAs using deep forests combined with positive-unlabeled learning methods
Zeng, X., Zhong, Y., Lin, W., & Zou, Q. (2019) · Briefings in Bioinformatics · doi:10.1093/bib/bbz080 · Cited by 139
Circular RNAs: Regulators of Cancer-Related Signaling Pathways and Potential Diagnostic Biomarkers for Human Cancers
Yang, Z., Xie, L., Han, L., Qu, X., Yang, Y., Zhang, Y., He, Z., Wang, Y., & Li, J. (2017) · Theranostics · doi:10.7150/thno.19016 · Cited by 140
“CircRNAs exhibit tissue- and developmental-specific expression and play crucial roles in multiple cellular processes, such as functioning as miRNA sponges by sequestering miRNA thereby affecting the stability of target mRNAs and dynamically regulating mRNA translation (Figure 1) [24-26].”
Background
RETRACTED: Exosome-mediated transfer of circRNA CircNFIX enhances temozolomide resistance in glioma
Ding, C., Yi, X., Wu, X., Bu, X., Wang, D., Wu, Z., Zhang, G., Gu, J., & Kang, D. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.03.002 · Cited by 140
Retracted
NUDT21 regulates circRNA cyclization and ceRNA crosstalk in hepatocellular carcinoma
Li, X., Ding, J., Wang, X., Cheng, Z., & Zhu, Q. (2019) · Oncogene · doi:10.1038/s41388-019-1030-0 · Cited by 138
The emerging role of circRNAs and their clinical significance in human cancers
Qian, L., Yu, S., Chen, Z., Meng, Z., Huang, S., & Wang, P. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.002 · Cited by 136
circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a
Si, X., Zheng, H., Wei, G., Li, M., Li, W., Wang, H., Guo, H., Sun, J., Li, C., Zhong, S., et al. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.06.024 · Cited by 135
SomamiR 2.0: a database of cancer somatic mutations altering microRNA–ceRNA interactions
Bhattacharya, A., & Cui, Y. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1220 · Cited by 133
Hsa_circ_0001361 promotes bladder cancer invasion and metastasis through miR-491-5p/MMP9 axis
Liu, F., Zhang, H., Xie, F., Tao, D., Xiao, X., Huang, C., Wang, M., Gu, C., Zhang, X., & Jiang, G. (2019) · Oncogene · doi:10.1038/s41388-019-1092-z · Cited by 135
Increased expression of circRNA_102231 in lung cancer and its clinical significance
Zong, L., Sun, Q., Zhang, H., Chen, Z., Deng, Y., Li, D., & Zhang, L. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.03.084 · Cited by 131
circCELSR1 (hsa_circ_0063809) Contributes to Paclitaxel Resistance of Ovarian Cancer Cells by Regulating FOXR2 Expression via miR-1252
Zhang, S., Cheng, J., Quan, C., Wen, H., Feng, Z., Hu, Q., Zhu, J., Huang, Y., & Wu, X. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.12.005 · Cited by 128
“These unique features make circRNA a research hotspot.(9) It is becoming increasingly apparent that dysregulated circRNAs are implicated in carcinogenesis and progression of numerous cancers, acting as either oncogenes or tumor suppressors.”
Background
Circular RNA hsa_circ_0004015 regulates the proliferation, invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway
Zhou, Y., Zheng, X. W., Xu, B., Chen, L., Wang, Q., Deng, H., & Jiang, J. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.157 · Cited by 127
Using circular RNA SMARCA5 as a potential novel biomarker for hepatocellular carcinoma
Li, Z., Zhou, Y., Yang, G., He, S., Qiu, X., Zhang, L., Deng, Q., & Zheng, F. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.02.001 · Cited by 126
Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma
Liu, W., Zhang, J., Zou, C., Xie, X., Wang, Y., Wang, B., Zhao, Z., Tu, J., Wang, X., Li, H., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000481650 · Cited by 124
Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31-5p/RAB27A axis
Bi, J., Liu, H., Cai, Z., Dong, W., Jiang, N., Yang, M., Huang, J., & Lin, T. (2018) · Aging · doi:10.18632/aging.101520 · Cited by 124
“The molecules are cyclized, lacking 5’ caps and 3’ poly (A) tails [6].”
Background
Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients, based on microarray chip technology
Zheng, F., Yu, X., Huang, J., & Dai, Y. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7638 · Cited by 123
“…the function of miRNAs by binding to miRNAs as sponges was reported (7). circRNAs, form as integral and conserved closed continuous loops structures wherein the 3' and 5' ends are interconnected, are a large novel class of non‑coding RNAs that is highly exist in the eukaryotic transcriptome (8,9).”
Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma
Zhao, S., Wang, J., Ouyang, S., Huang, Z., & Liao, L. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000491624 · Cited by 122

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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