Cited by 647Circular RNAs in diseasesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Circular RNA (circRNA) in Alzheimer’s disease (AD)

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Lukiw, Walter J.·2013·Frontiers in Genetics

DOI 10.3389/fgene.2013.00307PMC PMC3875874

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GENERAL COMMENTARY article Front. Genet., 31 December 2013 | https://doi.org/10.3389/fgene.2013.00307

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Circular RNAs are a large class of animal RNAs with regulatory potency
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., et al. (2013) · Nature · doi:10.1038/nature11928 · Cited by 7,990 · cited 1×
“Intrinsically resistant to exonucleolytic RNA decay, circRNAs appear to be enriched in mammalian brain tissues (Hansen et al., 2013; Memczak et al., 2013).”
Background
Natural RNA circles function as efficient microRNA sponges
Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., & Kjems, J. (2013) · Nature · doi:10.1038/nature11993 · Cited by 7,985
Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types
Salzman, J., Gawad, C., Wang, P. L., Lacayo, N., & Brown, P. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030733 · Cited by 2,239 · cited 1×
“Recently characterized, traditional methods of RNA detection and analysis requiring a free 5′ or 3′ ribonucleotide terminus may have significantly underestimated circRNA abundance and significance in eukaryotic cells (Salzman et al., 2012; Wilusz and Sharp, 2013; unpublished observations).”
Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943 · cited 1×
“…or AD groups (p > 0.05, ANOVA); a dashed horizontal line at 1.0 indicates homeostatic (control) ciRS-7 levels for ease of comparison; ∗p < 0.001 (ANOVA). contribute to the down-regulation of selective miRNA-7-sensitive messenger RNA (mRNA) targets (Cogswell et al., 2008; unpublished observations).”
BackgroundInfluential
A Circuitous Route to Noncoding RNA
Wilusz, J. E., & Sharp, P. A. (2013) · Science · doi:10.1126/science.1238522 · Cited by 531 · cited 1×
“Recently characterized, traditional methods of RNA detection and analysis requiring a free 5′ or 3′ ribonucleotide terminus may have significantly underestimated circRNA abundance and significance in eukaryotic cells (Salzman et al., 2012; Wilusz and Sharp, 2013; unpublished observations).”
Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling
Colangelo, V., Schurr, J., Ball, M. J., Pelaez, R. P., Bazan, N. G., & Lukiw, W. J. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10351 · Cited by 517
A Gene Expression Profile of Alzheimer's Disease
Loring, J. F., Wen, X., Lee, J. M., Seilhamer, J. J., & Somogyi, R. (2001) · DNA and Cell Biology · doi:10.1089/10445490152717541 · Cited by 300 · cited 2×
“…systems” and ambient up-regulation of specific inducible miRNAs may help explain the widely observed, generalized and progressive down-regulation of gene expression that is characteristic of the sporadic AD brain (Loring et al., 2001; Colangelo et al., 2002; Ginsberg et al., 2012; Lukiw, 2013).”
BackgroundInfluential
Deconstruction for Reconstruction: The Role of Proteolysis in Neural Plasticity and Disease
Bingol, B., & Sheng, M. (2011) · Neuron · doi:10.1016/j.neuron.2010.11.006 · Cited by 275
BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD)
Lukiw, W. J., Handley, P., Wong, L. J., & McLachlan, D. R. C. (1992) · Neurochemical Research · doi:10.1007/bf00968788 · Cited by 125 · cited 2×
“, 2013); detection was performed using a nonisotopic BrightStar BioDetect Kit (Ambion, Austin, TX; detection limit ∼100 fg) or by standard autoradiography (Lukiw et al., 1992); (B) AD ciRS-7 is significantly reduced to about 0.”
MethodInfluential
MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11)
Burmistrova, O., Goltsov, A. Y., Abramova, L. I., Каледа, В. Г., Александровна, О. В., & Rogaev, E. I. (2007) · Biochemistry (Moscow) · doi:10.1134/s0006297907050161 · Cited by 101 · cited 1×
“…but are also associated with a circRNA for miRNA-7 (ciRS-7), in the same tissues; ciRS-7 contains multiple, tandem anti-miRNA-7 sequences (Burmistrova et al., 2007; Hansen et al., 2013; Lukiw et al., 2013). ciRS-7 thereby acts as a kind of endogenous, competing, anti-complementary miRNA…”
Background

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Angiogenic circular RNAs: A new landscape in cardiovascular diseases
Zhang, T.-R., & Huang, W.-Q. (2020) · Microvascular Research · doi:10.1016/j.mvr.2020.103983 · Cited by 18
Localised Cdr1as activity is required for fear extinction memory
Zajaczkowski, E. L., Zhao, Q., Liau, W., Gong, H., Madugalle, S. U., Periyakaruppiah, A., Leighton, L. J., Musgrove, M. R. B., Ren, H., Davies, J., et al. (2023) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2023.107777 · Cited by 15
Competing endogenous RNA analysis reveals the regulatory potency of circRNA_036186 in HNSCC
Wang, W., Yang, Z. H., Zhang, Y.-J., Lu, P., Ni, Y., Sun, C., & Liu, F. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4499 · Cited by 17
“For instance, the circRNA ciRS-7 contains multiple and conservative miRNA-7 binding sites, thus acting as an efficient miRNA sponge to adsorb miRNA-7, and thus inhibiting its function (29).”
Circular RNAs in β-cell function and type 2 diabetes-related complications: a potential diagnostic and therapeutic approach
Ghasemi, H., Sabati, Z., Ghaedi, H., Salehi, Z., & Alipoor, B. (2019) · Molecular Biology Reports · doi:10.1007/s11033-019-04937-x · Cited by 16
“Recent studies suggest that the deregulation of circRNAs could be associated with human disorders such as coronary artery disease [73], neurodegenerative and autoimmune diseases [74, 75], and several types of cancer [76].”
Background
Going around in circles: deciphering the role of circular RNAs in neurodegenerative disease
Kondo, M., Mohan, A., & Mather, K. A. (2019) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000582 · Cited by 17
Advance in circular RNA modulation effects of heart failure
Jiang, L., Wang, X., Zhan, X., Kang, S., Liu, H., Luo, Y., & Lin, L. (2020) · Gene · doi:10.1016/j.gene.2020.100036 · Cited by 17
“…have been discovered and become a new field of various diseases, such as cardiovascular disease (Wang et al., 2016; Du et al., 2017), cancers (Chen et al., 2017; Shang et al., 2016; Wan et al., 2016), neurological dysfunction (Lukiw, 2013), autoimmune diseases (Luo et al., 2018) (Li et al., 2018).”
Background
The Secret Garden of Neuronal circRNAs
Gasparini, S., Licursi, V., Presutti, C., & Mannironi, C. (2020) · Cells · doi:10.3390/cells9081815 · Cited by 15
“AD Human HP CA1 and neo C from SAD patients CDR1as down miRNA sponge: CDR1as/miR-7 CDR1as-miR-7-UBE2A mRNA network [117,128]”
Background
Identification and characterization of melon circular RNAs involved in powdery mildew responses through comparative transcriptome analysis
Sun, J., Dong, Y., Wang, C., Xiao, S., Jiao, Z., & Gao, C. (2021) · PeerJ · doi:10.7717/peerj.11216 · Cited by 17
“CircRNAs have been studied in humans, mice, mosquitos, and sheep (Salzman et al., 2012; Gruner et al., 2016; Jiang et al., 2014; Li et al., 2017) with little attention given to plant circRNAs.”
Background
GATNNCDA: A Method Based on Graph Attention Network and Multi-Layer Neural Network for Predicting circRNA-Disease Associations
Ji, C., Liu, Z., Wang, Y., Ni, J., & Zheng, C.-H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168505 · Cited by 17
“Recent studies have shown that the circRNA level in the brain is associated with Alzheimer’s disease (AD) [16].”
Background
Construction of a circRNA-Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection
Liu, D.-B., He, Y., Chen, G.-J., Huang, H., Xie, X.-L., Lin, W.-J., & Peng, Z.-J. (2022) · International Journal of General Medicine · doi:10.2147/ijgm.s355906 · Cited by 16
“Recent evidence indicates that circRNAs are involved in various human diseases, such as cancer, 11 Alzheimer’s disease, 12 and cardiovascular diseases.”
Alzheimer’s disease pathogenetic progression is associated with changes in regulated retained introns and editing of circular RNAs
Maquera, K. A. A., Welden, J. R., Margvelani, G., Sardón, S. C. M., Hart, S. N., Robil, N., Hernandez, A. G., de la Grange, P., Nelson, P. T., & Stamm, S. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1141079 · Cited by 16
“MAP7 (ensconsin) is a microtubule associate protein that modulates microtubule function (Masson and Kreis, 1995; Bulinski et al., 2001).”
Background
Chronic Lead Exposure in Adult Mice: Associations with miR-671/CDR1as Regulation, NF-κB Signaling, and Alzheimer’s Disease-like Pathology
Qiao, M., Yang, H., Liu, L., Yu, T., Wang, H., Chen, X., Zhang, Y., Duan, A., Lyu, S., Wu, S., et al. (2024) · Toxics · doi:10.3390/toxics12060410 · Cited by 17
“The study also suggests that CDR1as could be used as an early biomarker for the diagnosis of AD based on the results of the assay and CDR1as’s special ring structure [36].”
Method
The transcriptomic landscape of neurons carrying PSEN1 mutations reveals changes in extracellular matrix components and non-coding gene expression
Corsi, G. I., Gadekar, V. P., Haukedal, H., Doncheva, N. T., Anthon, C., Ambardar, S., Palakodeti, D., Hyttel, P., Freude, K., Seemann, S. E., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105980 · Cited by 15
“The expression of CDR1as (ciRS-7, circBase: has_circ_0001946), a well-known circRNA gene acting as ceRNA in the mammalian brain, was previously reported by separate studies both as upregulated (Dube et al., 2019) and downregulated (Lukiw, 2013) in relation to AD compared to controls.”
Result
Circular RNAs and hereditary bone diseases
Zhai, N., Lu, Y., Wang, Y., Ren, X., & Han, J. (2018) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2018.01013 · Cited by 16
MSPCD: predicting circRNA-disease associations via integrating multi-source data and hierarchical neural network
Deng, L., Liu, D., Li, Y., Wang, R., Liu, J., Zhang, J., & Liu, H. (2022) · BMC Bioinformatics · doi:10.1186/s12859-022-04976-5 · Cited by 16
“In this section, to study the effect of the length of high-order feature on circRNA and disease associations prediction, we set the length of high-order feature to 8, 16, 32, 64, 128 for experimental comparison.”
Background
Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies
Meccariello, R., Bellenchi, G. C., Pulcrano, S., D’Addario, S. L., Tafuri, D., Mercuri, N. B., & Guatteo, E. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1328269 · Cited by 14
“…altered expression in disease like brain-tumor growth, traumatic brain injury or acute and chronic neurodegenerative disorders has been reported (Lukiw, 2013; Chen et al., 2016; Errichelli et al., 2017; Huang et al., 2018; Xu et al., 2018; Dube et al., 2019; Mehta et al., 2020; Li et al.,…”
Background
Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis
Wang, R., Feng, Y., Xu, H. K., Huang, H., Zhao, S., Wang, Y., Li, H., Cao, J., Xu, G., & Huang, S. (2020) · Journal of International Medical Research · doi:10.1177/0300060520978015 · Cited by 15
Predicting circRNA-Disease Associations Based on Deep Matrix Factorization with Multi-source Fusion
Xie, G., Chen, H., Sun, Y., Gu, G., Lin, Z., Wang, W., & Li, J. (2021) · Interdisciplinary Sciences Computational Life Sciences · doi:10.1007/s12539-021-00455-2 · Cited by 15
CircRNA as CeRNA mediated by microRNA may be involved in goat lactation
Ma, D., Zhao, Y. M., Yu, S., Zhang, H., Cheng, M. Y., Cao, H., Li, Q., & Min, L. (2019) · Small Ruminant Research · doi:10.1016/j.smallrumres.2018.12.009 · Cited by 15
hsa_circ_0071106 can be used as a diagnostic marker for type 2 diabetes
Yingying, Z., Yongji, Y., Qiuting, C., Rifang, L., & Zhuanping, Z. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.52575 · Cited by 17
Exploring the Therapeutic Potential of Noncoding RNAs in Alzheimer’s Disease
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Potential biomarkers of aortic dissection based on expression network analysis
Feng, J., Hu, Y., Peng, P., Li, J., & Ge, S. (2023) · BMC Cardiovascular Disorders · doi:10.1186/s12872-023-03173-3 · Cited by 14
The Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer’s Disease
Abed, S., Ebrahimi, A., Fattahi, F., Kouchakali, G., Khaniani, M. S., & Derakhshan, S. M. (2024) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02262-y · Cited by 16
“This further decreases ciRS-7, increasing the expression of miR-7, which in turn inhibits another critical AD target, ubiquitin protein ligase A, required for the clearance of toxic amyloid peptides from AD brains (UBE2A) (Lukiw 2013). ciRS-7 has been implicated in AD pathology by regulating the protein levels of APP…”
The circRNA circ-Nbea participates in regulating diabetic encephalopathy
Liu, J., Deng, Z., Yu, Z., Zhou, W., & Yuan, Q. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147702 · Cited by 15
Analysis of the circRNA and T-UCR populations identifies convergent pathways in mouse and human models of Rett syndrome
Soares, E. S., Obiols-Guardia, A., Jorge-Torres, O. C., Oliveira-Mateos, C., Soler, M., Ramesh-Kumar, D., Setién, F., van Rossum, D., Pascual‐Alonso, A., Xiol, C., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.12.030 · Cited by 14
Emerging Roles of Circular RNAs in Vascular Smooth Muscle Cell Dysfunction
Pu, Z., Lu, J., & Yang, X. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2021.749296 · Cited by 14
“…that deregulated expression of circRNAs is closely related to different types of diseases, such as degenerative diseases, tumor, congenital diseases, endocrine diseases and cardiovascular diseases (Lukiw, 2013; Li et al., 2019a; Chen et al., 2021a; Li et al., 2021; Papatsirou et al., 2021).”
Background
Interplay between circular RNA, microRNA, and human diseases
Kour, B., Gupta, S., Singh, R., Sophiarani, Y., & Paul, P. (2022) · Molecular Genetics and Genomics · doi:10.1007/s00438-022-01856-8 · Cited by 14
“2013; Lukiw 2013).”
BackgroundInfluential
Expression of circular RNAs in the vascular dementia rats
Huang, Y., Liao, X., Luo, J., Liu, H., Zhong, S., & Chen, J. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135087 · Cited by 14
Correlation between serum circRNA and thyroid micropapillary carcinoma with cervical lymph node metastasis
Yang, W., Bai, C., Zhang, L., Li, Z., Tian, Y., Yang, Z., Wang, L., & Wu, W. (2020) · Medicine · doi:10.1097/md.0000000000023255 · Cited by 14
RETRACTED ARTICLE: Circular RNA testis-expressed 14 overexpression induces apoptosis and suppresses migration of ox-LDL-stimulated vascular smooth muscle cells via regulating the microRNA 6509-3p/thanatos-associated domain-containing apoptosis-associated protein 1 axis
Kou, L., Yang, N., Dong, B., Yang, J., Song, Y., Li, Y., & Qin, Q. (2022) · Bioengineered · doi:10.1080/21655979.2022.2070582 · Cited by 13
“They have potent regulatory effects [11] on various human diseases such as Alzheimer’s disease [12], cancers [13], nonalcoholic steatohepatitis [14], and cardiovascular diseases [15].”
Background
Retracted
Circ-AMOTL1 enhances cardiac fibrosis through binding with EIF4A3 and stabilizing MARCKS expression in diabetic cardiomyopathy
Yang, Y., Yang, H., & Yang, C. (2023) · Cellular Signalling · doi:10.1016/j.cellsig.2023.110853 · Cited by 13
PlantCircRNA: a comprehensive database for plant circular RNAs
Shutian, H., Bing, J., Zhong, Y., Zheng, X., Zhou, Z., Wang, Y., Hu, J., & Sun, X. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae709 · Cited by 13
Hepatitis C virus core impacts expression of miR122 and miR204 involved in carcinogenic progression via regulation of TGFBRAP1 and HOTTIP expression
Wang, X., Peng, J., Wang, J., Li, M., Wu, D., Wu, S., Liao, J., & Dou, J. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s149254 · Cited by 13
“After washing the slides, the arrays were scanned by the Agilent Scanner G2505C and the same steps as that of the protocol of lncRNA array assay were followed.(17,20,21)”
circ2GO: A Database Linking Circular RNAs to Gene Function
Lyu, Y., Caudron‐Herger, M., & Diederichs, S. (2020) · Cancers · doi:10.3390/cancers12102975 · Cited by 13
The identification of circular RNAs from peripheral blood mononuclear cells in systemic lupus erythematosus
Zheng, F., Yu, X., Tang, D., Hong, X., Zhang, X., Liu, D. J., & Dai, Y. (2021) · BMC Medical Genomics · doi:10.1186/s12920-021-00919-w · Cited by 13
“CircRNAs have been implicated in neurological disorders such as Alzheimer’s disease [9] as well as in pancreatic carcinoma [10] and esophageal squamous cell carcinoma [11].”
Background
Circ_0000591 served as endogenous RNA for miR-326 to promote progression of cholangiocarcinoma via the TLR4/MyD88/IL6 axis
Xiao, F., Xu, F., Zhang, H., & Shuai, X. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.02.073 · Cited by 13
Profile of TREM2-Derived circRNA and mRNA Variants in the Entorhinal Cortex of Alzheimer’s Disease Patients
Urdánoz‐Casado, A., de Gordoa, J. S., Robles, M., Roldán, M., Zelaya, M. V., Blanco‐Luquin, I., & Mendióroz, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147682 · Cited by 13
The hidden players: Shedding light on the significance of post-translational modifications and miRNAs in Alzheimer's disease development
Singh, R. J., Hussain, J., Kaur, A., Jamdare, B. G., Pathak, D., Garg, K., Kaur, R., Shankar, S., & Sunkaria, A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102002 · Cited by 14
FcircSEC: An R Package for Full Length circRNA Sequence Extraction and Classification
Hossain, M. T., Peng, Y., Feng, S., & Wei, Y. (2020) · International Journal of Genomics · doi:10.1155/2020/9084901 · Cited by 14
“Different studies suggest that circRNAs are important biomarkers for different cancers [29–31] and autoimmune diseases [32, 33], a potential noninvasive diagnosis for atherosclerosis [34], disorders of the central neural diseases [35], degenerative diseases [17], and cancers [10, 36].”
Background
Identification and Characterization of Circular RNA as a Novel Regulator and Biomarker in Preterm Birth
Ran, Y., Yin, N., Huang, D., Zhao, Y., Yang, J., Zhang, H., & Qi, H. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.566984 · Cited by 13
“…interest and study on circRNA in various diseases since 2013 when it was first reported to be related to the occurrence of Alzheimer’s disease (AD), due to its stable nature and its ability to regulate a variety of biological pathways through the ceRNA mechanism (Lukiw, 2013; Zhong et al., 2018).”
Background
Downregulation of hsa_circ_0006220 and its correlation with clinicopathological factors in human breast cancer
Liu, C., Chen, M., & Shi, Y. X. (2021) · Gland Surgery · doi:10.21037/gs-21-42 · Cited by 13
“Accumulating evidence has illustrated that circRNAs can combine with and inhibit micro RNAs (miRNAs) to exert biological effects by acting as a miRNA “sponge” or can serve as transcription regulators (3,5-7).”
Background
Exposure to methamphetamine exacerbates motor activities and alters circular RNA profile of cerebellum
Boroujeni, M. E., Nasrollahi, A., Boroujeni, P. B., Fadaei-Fathabadi, F., Farhadieh, M., Tehrani, A. M., Nakhaei, H., Sajedian, A. M., Peirouvi, T., & Aliaghaei, A. (2020) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2020.05.010 · Cited by 12
Differentially Expressed Circular RNA Profile in an Intracranial Aneurysm Group Compared with a Healthy Control Group
Ma, Y., Zhang, B.-Q., Zhang, D., Wang, S., Li, M., & Zhao, J. (2021) · Disease Markers · doi:10.1155/2021/8889569 · Cited by 12
“It has been shown that circRNA ciRS7/CDR1as is associated with amyloid peptide clearance by regulating miRNA miR-7 [36, 37].”
Background
CircSYNDIG1 ameliorates stress-induced abnormal behaviors by suppressing miR-344-5p in mice
Wang, X., Song, H. S., Du, Y., Zhao, Y., Fu, Y., Meng, Q., Gao, Y., Gong, M., Li, S., Wang, S., et al. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.02.010 · Cited by 13
“Downregulated ciRS-7 in hippocampus contributes to Alzheimer’s disease through miR-7 (Lukiw, 2013).”
Background
Regulation of LncRNAs and microRNAs in neuronal development and disease
Xuan, C., Yang, E., Zhao, S., Xu, J., Li, P., Zhang, Y., Jiang, Z., & Ding, X. (2023) · PeerJ · doi:10.7717/peerj.15197 · Cited by 12
“…miR-100 Haramati et al. (2010) circRNA AD ciRS-7 Lukiw (2013) T-UCR Idiopathic neurodevelopmental disease T-UCRs uc.195, uc.392, uc.46 and uc.222 Lukiw (2013) snoRNA PWS snoRNA cluster at 15q11–q13 imprinted locus Kishore & Stamm (2006), Horsthemke & Wagstaff (2008) and Sahoo et al.…”
Background
Adipose Tissue Exosome circ_sxc Mediates the Modulatory of Adiposomes on Brain Aging by Inhibiting Brain dme-miR-87-3p
Li, Q., Wang, L., Tang, C., Wang, X., Yu, Z., Ping, X., Ding, M., & Zheng, L. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03516-3 · Cited by 12
“Currently, circRNAs have been shown to have a variety of bioregulatory functions, and critically, their role as competitors to mRNAs in binding to microRNAs (miRNAs) and thereby regulating gene expression has been confirmed by several studies [17–19].”
The Antisense Transcriptome and the Human Brain
Mills, J. D., Chen, B. J., Ueberham, U., Arendt, T., & Janitz, M. (2015) · Journal of Molecular Neuroscience · doi:10.1007/s12031-015-0694-3 · Cited by 13
The Role of Noncoding RNAs in Neurodevelopmental Disorders: The Case of Rett Syndrome
Obiols-Guardia, A., & Guil, S. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-53889-1_2 · Cited by 12
RNA-Seq Profiling of Circular RNAs During Development of Hindgut in Rat Embryos With Ethylenethiourea-Induced Anorectal Malformations
Li, S. Y., Wang, C. Y., Yun, X., Tang, X. B., Yuan, Z., & Bai, Y. Z. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.605015 · Cited by 12
“In the present study, circRNA expression patterns in the hindguts of rat embryos with ETU-induced ARMs were profiled from gestational day (GD)14 to GD16, the key time period for anorectal development (Qi et al., 2002; Bai et al., 2004; Macedo et al., 2007).”
Background
Genome-Wide Differential Expression Profiling of Pulmonary circRNAs Associated With Immune Reaction to Pasteurella multocida in Goats
Chen, Q., Zhang, Z., Chen, S., Chen, J., Cheng, Y., Liu, A., Li, B., Chen, Z., Zheng, Y., Ga, M., et al. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.615405 · Cited by 12
The emerging role of circular RNAs in spinal cord injury
Peng, P., Yu, H., Li, Y., Huang, J., Yao, S.-Y., Xing, C., Liu, W., Zhang, B., & Feng, S. (2021) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2021.06.001 · Cited by 13
Expression and Secretion of Circular RNAs in the Parasitic Nematode, Ascaris suum
Minkler, S. J., Loghry, H. J., Sondjaja, N. A., & Kimber, M. J. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.884052 · Cited by 11
“CDR1as has been linked to several diseases such as Alzheimer’s disease (Lukiw, 2013) and hepatocellular carcinoma (Yu et al.”
Background
Commentary: FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
Verheijen, B. M., & Pasterkamp, R. J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00412 · Cited by 13
“In addition, circRNAs have been associated with neural disorders, such as Alzheimer’s disease (Lukiw, 2013).”
Background
RNA sequencing reveals the circular RNA expression profiles of the infrapatellar fat pad/synovium unit
Jiang, T., Lu, Y., Chen, Z., Lin, X., Zhang, J., Shan, J., Lü, C., Zhao, C., Xu, X., & Liu, W. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-5739 · Cited by 11
Whole-Genome-Based Web Genomic Resource for Water Buffalo (Bubalus bubalis)
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“The functions of circRNAs are not well known but still it is reported that they play a significant role in post-transcriptional regulation of gene expression (Lukiw, 2013).”
Background
Parkinson’s Disease and MicroRNAs: A Duel Between Inhibition and Stimulation of Apoptosis in Neuronal Cells
Saadh, M. J., Faisal, A., Adil, M., Zabibah, R. S., Mamadaliev, A. M., Jawad, M. J., Alsaikhan, F., & Farhood, B. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04111-w · Cited by 11
Altered expression of circular RNA in human dental pulp cells during odontogenic differentiation
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Arabidopsis thaliana cbp80, c2h2, and flk Knockout Mutants Accumulate Increased Amounts of Circular RNAs
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Sophisticated Gene Regulation for a Complex Physiological System: The Role of Non-coding RNAs in Photoreceptor Cells
Carrella, S., Banfi, S., & Karali, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.629158 · Cited by 12
“They are involved in numerous biological processes and are differentially expressed in various diseases (Ghosal et al., 2013; Lukiw, 2013; Li et al., 2015; Peng et al., 2015; Zhao and Shen, 2017), including diabetic retinopathy, highlighting their potential as biomarkers and as predictors of…”
Background
Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer
Chu, J., Fang, X., Sun, Z., Gai, L., Dai, W., Li, H., Yan, X., Du, J., Zhang, L., Zhao, L., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.801319 · Cited by 11
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Regulation of neuronal circHomer1 biogenesis by PKA/CREB/ERK-mediated pathways and effects of glutamate and dopamine receptor blockade.Preprint
Mellios, N., Papageorgiou, G., Gorgievski, V., Maxson, G., Hernandez, M., Otero, M. P., Varangis, M., Dell’Orco, M., Perrone‐Bizzozero, N. I., & Tzavara, E. T. (2024) · Research Square · doi:10.21203/rs.3.rs-3547375/v1 · Cited by 11
RETRACTED ARTICLE: Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition
Su, Q., Shen, H., Gu, B., & Zhu, N. (2021) · Bioengineered · doi:10.1080/21655979.2021.1974805 · Cited by 10
Retracted
Differential expression of circular RNAs in the proximal and distal segments of the sciatic nerve after injury
Sohn, E. J., & Park, H. T. (2019) · Neuroreport · doi:10.1097/wnr.0000000000001371 · Cited by 10
Hsa_circ_0054633 association of C peptide is related to IL‐17 and TNF‐α in patients with diabetes mellitus receiving insulin treatment
Dai, H., Hu, F., Yang, X., Hu, P., Chu, Y., & Bu, S. (2021) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.23856 · Cited by 10
Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer
Kong, Z., Lu, Y., Wan, X., Luo, J., Li, D., Huang, Y., Wang, C., Li, Y., & Xu, Y. (2021) · Life · doi:10.3390/life11101096 · Cited by 10
RNA Biological Characteristics at the Peak of Cell Death in Different Hereditary Retinal Degeneration Mutants
Wei, C., Li, Y., Feng, X., Hu, Z., Paquet‐Durand, F., & Jiao, K. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.728791 · Cited by 10
“While circRNAs participate in retinal development, abnormally expressed circRNAs may cause various neurological disorders and diabetic retinopathy (Lukiw, 2013; Shan et al., 2017).”
Background
Targeting circRNA-MAP4K2 for the treatment of diabetes-induced retinal vascular dysfunction
Ma, C., Shi, Z.-H., Han, X., Liu, C., Yan, B., & Du, J. (2022) · Aging · doi:10.18632/aging.204215 · Cited by 11
Functional Characterisation of the Circular RNA, circHTT(2-6), in Huntington’s Disease
Gantley, L., Stringer, B. W., Conn, V. M., Ootsuka, Y., Holds, D. A., Slee, M., Aliakbari, K., Kirk, K., Ormsby, R. J., Webb, S. T., et al. (2023) · Cells · doi:10.3390/cells12091337 · Cited by 10
Identification of aberrant circular RNA expression and its potential clinical value in primary great saphenous vein varicosities
Zhang, W., Li, L., Si, Y., Shi, Z., Zhu, T., Zhuang, S., & Fu, W. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.03.156 · Cited by 10
Comprehensive analysis of circRNAs expression profiles in different periods of MDBK cells infected with bovine viral diarrhea virus
Li, C., Li, X., Hou, X., Ni, W., Zhang, M., Li, H., Xu, Y., Hazi, W., Ma, Q., Zhang, Y., et al. (2019) · Research in Veterinary Science · doi:10.1016/j.rvsc.2019.05.005 · Cited by 10
Circular RNAs and Its Biological Functions in Health and Disease
Sağlam, A. S. Y., Alp, E., & Önen, H. İ. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88764 · Cited by 10
Upregulated hsa_circ_0000129 expression promotes proliferation and migration of breast cancer cells
Zhang, Z., Shi, Z., Zhang, S., Lu, Q., Wei, H., Wu, X., & Han, L. (2021) · Oncology Letters · doi:10.3892/ol.2021.12500 · Cited by 10
Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in postmenopausal osteoporosis
Diao, W., Wang, Y., Zhang, J., Shao, H., Huang, Y., & Jin, M. (2021) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-021-02604-1 · Cited by 10
Circular noncoding RNA hsa_circ_0005986 as a prognostic biomarker for hepatocellular carcinoma
Kim, G., Han, J., Park, S. Y., Tak, W. Y., Kweon, Y.-O., Lee, Y. R., Han, Y. S., Park, J. G., Kang, M. K., Lee, H. W., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-94074-y · Cited by 10
Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction
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“The dysregulation of circRNAs was involved in the onset and development of neurodegenerative diseases such as Alzheimer’s disease, schizophrenia, autism, depression and other mental diseases (Li et al., 2011; Lukiw, 2013; Liu et al., 2020; Mehta et al., 2020; Zimmerman et al., 2020).”
Background
The Biological Functions of Non-coding RNAs: From a Line to a Circle
Wu, N., & Yang, B. B. (2015) · Discoveries · doi:10.15190/d.2015.40 · Cited by 10
Prenatal alcohol exposure results in brain region- and sex-specific changes in circHomer1 expression in adult mouse brain
Papageorgiou, G., Amoah, S. K., Pierotti, C. E., Otero, M. P., Eckel, S. E., Coffey, K., Allan, A. M., Caldwell, K. K., & Mellios, N. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1087950 · Cited by 10
“Numerous studies have suggested the importance of circRNAs for brain development and function and their relevance for neurodevelopmental and psychiatric disorders (Lukiw, 2013; Mehta et al., 2020; Zimmerman et al., 2020; Li M. L. et al., 2021; Hafez et al., 2022).”
Background
Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond
Statsenko, Y. A., Kuznetsov, N. V., Morozova, D., Liaonchyk, K., Simiyu, G. L., Smetanina, D., Kashapov, A., Meribout, S., Gorkom, K., Hamoudi, R., et al. (2023) · Cells · doi:10.3390/cells12202451 · Cited by 8
“For example, CIRS-7 potentially functions as a sponge for MIR7-1 [154] and its level is dramatically reduced in the AD brain [155].”
Background
An interpretable Alzheimer’s disease oligogenic risk score informed by neuroimaging biomarkers improves risk prediction and stratification
Suh, E. H., Lee, G., Jung, S., Wen, Z., Bao, J., Nho, K. T., Huang, H., Davatzikos, C. A., Saykin, A. J., Thompson, P. M., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1281748 · Cited by 8
“Although there is little information specific to EFCAB11 in AD, studies have found connections of alternative circRNAs to AD, such as dysregulated cIRS-7-miR-7 interaction in the hippocampus of AD patients (Lukiw, 2013; Zhao et al., 2022).”
Background
Plasma Circular RNAs as Biomarkers for Breast Cancer
Tierno, D., Grassi, G., Zanconati, F., Dapas, B., & Scaggiante, B. (2024) · Biomedicines · doi:10.3390/biomedicines12040875 · Cited by 10
Current advances in our understanding of circular RNA (circRNA) in Alzheimer’s disease (AD); the potential utilization of synthetic circRNAs as a therapeutic strategy in the clinical management of AD
Zhao, Y., Jaber, V. R., & Lukiw, W. J. (2022) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2022.983030 · Cited by 9
“To date the best characterized circRNA functions are associated with miRNA regulation (Salzman et al., 2012; Hansen et al., 2013; Lukiw 2013; Memczak et al., 2013; Salzman et al., 2013; Jeck and Sharpless 2014; Zhao et al., 2016; Akhter 2018; Nisar et al., 2021; Rybak-Wolf and Plass, 2021; Sharma…”
BackgroundInfluential
Brain-protective mechanisms of autophagy associated circRNAs: Kick starting self-cleaning mode in brain cells via circRNAs as a potential therapeutic approach for neurodegenerative diseases
Basri, R., Awan, F. M., Yang, B. B., Awan, U. A., Obaid, A., Naz, A., Ikram, A., Khan, S., Haq, I. U., Khan, S. N., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1078441 · Cited by 9
“In another study authors reported that via sponging miR-7, circRNA s-7 promoted the expression of important genes associated with PD and AD (Lukiw, 2013).”
Background
Comprehensive expression profiles of CircRNAs, LncRNAs, and mRNAs in PBMCs from patients with the ossification of the posterior longitudinal ligament
Jiang, N., Zhang, K., Shang, J., Wang, B., Zhong, J., Wu, B., Li, H., Xu, X., & Lu, H. (2021) · Molecular Omics · doi:10.1039/d1mo00060h · Cited by 9
Differentially Expressed Circular RNAs and Their Therapeutic Mechanism in Non-segmental Vitiligo Patients Treated With Methylprednisolone
Zhang, J., Liang, N., Cao, Y., & Li, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.839066 · Cited by 9
Reconstruction of Full-Length circRNA Sequences Using Chimeric Alignment Information
Hossain, M. T., Zhang, J., Reza, M. S., Peng, Y., Feng, S., & Wei, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126776 · Cited by 8
circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR‐92a‐2‐5p/KLLN Pathway
Gao, L., Shao, X., Yue, Q., Wu, W., Yang, X., He, X., Li, L., Hou, F., & Zhang, R. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9970272 · Cited by 9
The role of CDR1as/ciRS-7 in cardio-cerebrovascular diseases
Shao, Y., Xu, J., Liang, B., Zhang, S., Chen, W., Wang, Y., & Xing, D. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115589 · Cited by 9
Roles of Circular RNAs And Their Interactions With MicroRNAs in Human Disorders
Sun, J. (2018) · Clinical surgery research communications · doi:10.31491/csrc.2018.6.012 · Cited by 8
Hsa_ Circ_0005044 Promotes Osteo/Odontogenic Differentiation of Dental Pulp Stem Cell Via Modulating miR-296-3p/FOSL1
Liu, Z., Li, S., Xu, S., Ku, N. E. B. Y. A. B. D. X., Wen, J., Zeng, X., Shen, X., & Xu, P. (2022) · DNA and Cell Biology · doi:10.1089/dna.2022.0394 · Cited by 8
“Several studies to date have provided strong evidence that circRNAs can both regulate gene expression and serve as ideal biomarkers for the diagnosis of particular disease states (Hansen et al, 2013; Li et al, 2015b; Lukiw, 2013).”
Engineering circular RNA for molecular and metabolic reprogramming
Sharma, N. K., Dwivedi, P., Bhushan, R., Maurya, P. K., Kumar, A., & Dakal, T. C. (2024) · Functional & Integrative Genomics · doi:10.1007/s10142-024-01394-z · Cited by 8
“These studies have suggested that circRNAs could serve as promising targets for potential Alzheimer’s Disease therapies.”
Influential
The involvement of hsa_circ_0000417 in the development of hypospadias by regulating AR
Chen, C., Jian, Y.-Y., Zhao, X., Liu, Y., & Xie, Q. (2020) · Differentiation · doi:10.1016/j.diff.2020.09.003 · Cited by 8
Bibliometric Analysis of Global Circular RNA Research Trends from 2007 to 2018.
Wu, R., Guo, F., Wang, C., Qian, B., Shen, F., Huang, F., & Xu, W. (2021) · PubMed Central · doi:10.22074/cellj.2021.7143 · Cited by 8
Identification of Circular RNAs Related to Vascular Endothelial Proliferation, Migration, and Angiogenesis After Spinal Cord Injury Using Microarray Analysis in Female Mice
Ye, X., Chen, Y., Wang, J., Chen, J., Yao, Y., Wang, L., & Zhao, F. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.666750 · Cited by 8
Potential roles of hsa_circ_000839 and hsa_circ_0005986 in breast cancer
Firoozi, Z., Mohammadisoleimani, E., Shahi, A., Mansoori, H., Naghizadeh, M. M., Bastami, M., Nariman‐Saleh‐Fam, Z., Daraei, A., Raoofat, A., & Mansoori, Y. (2022) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24263 · Cited by 8
RNA-Seq profiling of circular RNAs in human colorectal cancer 5-fluorouracil resistance and potential biomarkers
Cheng, P., Liu, Y., Zhang, S., Lu, L., Zhou, W., Hu, D., Xu, H.-C., & Ji, G. (2022) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v14.i3.678 · Cited by 8
Chronic constriction injury-induced changes in circular RNA expression profiling of the dorsal root ganglion in a rat model of neuropathic pain
Xiong, W., Wei, M., Zhang, L., Wang, J., Liu, F., & Wang, Z. (2022) · BMC Neuroscience · doi:10.1186/s12868-022-00745-5 · Cited by 8
“Alterations in universal circRNA expression have been identified in various diseases, including cancer [37], Alzheimer’s disease [38], and type 2 diabetes [39].”
Background
DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain
Liu, X., Jin, T. Y., Tao, Y., Zhang, M., Zheng, H., Liu, Q., Yang, K., Wei, R., Li, S., Huang, Y. M., et al. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01082-x · Cited by 8
Circular RNAs: A New Approach to Multiple Sclerosis
Sciaccotta, R., Murdaca, G., Caserta, S., Rizzo, V., Gangemi, S., & Allegra, A. (2023) · Biomedicines · doi:10.3390/biomedicines11112883 · Cited by 8
“…through the transfer of lipids, proteins, and genetic material between cells; in fact, their involvement in extracellular vesicle (EV)-mediated communication has been demonstrated in the modulation of multiple biological processes (Figure 2), such as the immune system’s response [96,97].”
Background
Non-coding RNAs as key players in the neurodegenerative diseases: Multi-platform strategies and approaches for exploring the Genome’s dark matter
Almohaimeed, H. M., Assiri, R., Althubaiti, E. H., Aggad, W. S., Shaheen, S. Y., Shaheen, M. Y., Batarfi, M. A., Alharbi, N. A., Alshehri, A. M., & Alkhudhairy, B. S. M. (2023) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2023.102236 · Cited by 6

Authors: Lukiw, W. J.
Affiliations: Louisiana State University (US)
Corresponding author: Lukiw, Walter J.
ORCID: Lukiw, Walter J.
Venue: Frontiers in Genetics
Publisher: Frontiers Media SA
Published: 2013
Volume: 4
Pages: 307-307
ISSN: 1664-8021 (ISSN-L)
DOI: 10.3389/fgene.2013.00307
PMC: PMC3875874
OpenAlex: W2095799789
Cited by: 636
References: 14
Citations by year: 2026: 9 · 2025: 12 · 2024: 25 · 2023: 48 · 2022: 57 · 2021: 85 · 2020: 103 · 2019: 88 · 2018: 89 · 2017: 66 · 2016: 32 · 2015: 14 · 2014: 6
FWCI: 7.76
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Instytut Medycyny Doswiadczalnej i Klinicznej im. M. Mossakowskiego, Polskiej Akademii Nauk
National Institute on Aging (AG038834, NIA AG038834, R01AG038834)
National Eye Institute (NEI-EY-006311, R01EY006311, EY-006311)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: circular RNA, Alzheimer's disease, non-coding RNA, RNA circularization

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Circular RNA (circRNA) in Alzheimer’s disease (AD)

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