Skip to main content
SpringerLink
Log in

Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

References

  1. Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N, Giusti S, Hanan M, Behm M et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58(5):870–885. https://doi.org/10.1016/j.molcel.2015.03.027

    Article  PubMed  CAS  Google Scholar 

  2. Kyzar EJ, Bohnsack JP, Pandey SC (2022) Current and future perspectives of noncoding RNAs in brain function and neuropsychiatric disease. Biol Psychiatry 91(2):183–193. https://doi.org/10.1016/j.biopsych.2021.08.013

    Article  PubMed  CAS  Google Scholar 

  3. Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J (2019) The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 20(11):675–691. https://doi.org/10.1038/s41576-019-0158-7

    Article  PubMed  CAS  Google Scholar 

  4. Bu Q, Long H, Shao X, Gu H, Kong J, Luo L, Liu B, Guo W et al (2019) Cocaine induces differential circular RNA expression in striatum. Transl Psychiatry 9(1):199. https://doi.org/10.1038/s41398-019-0527-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Floris G, Gillespie A, Zanda MT, Dabrowski KR, Sillivan SE (2022) Heroin regulates orbitofrontal circular RNAs. Int J Mol Sci 23(3). https://doi.org/10.3390/ijms23031453

  6. Mahmoudi E, Fitzsimmons C, Geaghan MP, Shannon Weickert C, Atkins JR, Wang X, Cairns MJ (2019) Circular RNA biogenesis is decreased in postmortem cortical gray matter in schizophrenia and may alter the bioavailability of associated miRNA. Neuropsychopharmacology 44(6):1043–1054. https://doi.org/10.1038/s41386-019-0348-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Yu H, Xie B, Zhang J, Luo Y, Galaj E, Zhang X, Shen Q, Liu Y et al (2021) The role of circTmeff-1 in incubation of context-induced morphine craving. Pharmacol Res 170:105722. https://doi.org/10.1016/j.phrs.2021.105722

    Article  PubMed  CAS  Google Scholar 

  8. Shen Q, Xie B, Galaj E, Yu H, Li X, Lu Y, Zhang M, Wen D et al (2022) CircTmeff-1 in the nucleus accumbens regulates the reconsolidation of cocaine-associated memory. Brain Res Bull 185:64–73. https://doi.org/10.1016/j.brainresbull.2022.04.010

    Article  PubMed  CAS  Google Scholar 

  9. Chafee MV, Heilbronner SR (2022) Prefrontal cortex. Curr Biol 32(8):R346–R351. https://doi.org/10.1016/j.cub.2022.02.071

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Volkow ND, Michaelides M, Baler R (2019) The neuroscience of drug reward and addiction. Physiol Rev 99(4):2115–2140. https://doi.org/10.1152/physrev.00014.2018

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Yang X, Wen Y, Zhang Y, Gao F, Yang J, Yang Z, Yan C (2020) Dynamic changes of cytoskeleton-related proteins within reward-related brain regions in morphine-associated memory. Front Neurosci 14:626348. https://doi.org/10.3389/fnins.2020.626348

    Article  PubMed  Google Scholar 

  12. Franklin K, Paxinos G, Keith B (2008) The mouse brain in stereotaxic coordinates. Rat Brain in Stereotaxic Coordinates 3(2):6

    Google Scholar 

  13. Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL (2016) Transcript-level expression analysis of RNA-seq experiments with HISAT. StringTie and Ballgown Nat Protoc 11(9):1650–1667. https://doi.org/10.1038/nprot.2016.095

    Article  PubMed  CAS  Google Scholar 

  14. Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol 11(10):R106. https://doi.org/10.1186/gb-2010-11-10-r106

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14(4):R36. https://doi.org/10.1186/gb-2013-14-4-r36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S et al (2008) KEGG for linking genomes to life and the environment. Nucleic Acids Res 36(Database issue):D480–D484

    CAS  Google Scholar 

  17. Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P (2015) The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst 1(6):417–425

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Zhong S, Feng J (2022) CircPrimer 2.0: a software for annotating circRNAs and predicting translation potential of circRNAs. BMC Bioinformatics 23(1):215. https://doi.org/10.1186/s12859-022-04705-y

    Article  PubMed Central  CAS  Google Scholar 

  19. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS (2003) MicroRNA targets in Drosophila. Genome Biol 5(1):R1

    Article  PubMed  PubMed Central  Google Scholar 

  20. Krüger J, Rehmsmeier M (2006) RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res 34(Web Server issue):W451–W454

    Article  PubMed  PubMed Central  Google Scholar 

  21. Agarwal V, Bell GW, Nam J-W, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. Elife 4. https://doi.org/10.7554/eLife.05005

  22. Sticht C, De La Torre C, Parveen A, Gretz N (2018) miRWalk: an online resource for prediction of microRNA binding sites. PLoS ONE 13(10):e0206239. https://doi.org/10.1371/journal.pone.0206239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Gruber AR, Lorenz R, Bernhart SH, Neuböck R, Hofacker IL (2008) The Vienna RNA websuite. Nucleic Acids Res 36(Web Server issue):W70–W74. https://doi.org/10.1093/nar/gkn188

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Doyle TM, Hutchinson MR, Braden K, Janes K, Staikopoulos V, Chen Z, Neumann WL, Spiegel S et al (2020) Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents. J Neuroinflammation 17(1):314. https://doi.org/10.1186/s12974-020-01975-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Wang Y-J, Yu C, Wu W-W, Ju Y-Y, Liu Y, Xu C, Long J-D, Zan G-Y et al (2021) Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory. Mol Psychiatry 26(11):6218–6236. https://doi.org/10.1038/s41380-021-01111-3

    Article  PubMed  CAS  Google Scholar 

  26. Ferrer-Alcón M, García-Fuster MJ, La Harpe R, García-Sevilla JA (2004) Long-term regulation of signalling components of adenylyl cyclase and mitogen-activated protein kinase in the pre-frontal cortex of human opiate addicts. J Neurochem 90(1):220–230

    Article  PubMed  Google Scholar 

  27. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102(43):15545–15550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Kauer JA, Malenka RC (2007) Synaptic plasticity and addiction. Nat Rev Neurosci 8(11):844–858

    Article  PubMed  CAS  Google Scholar 

  29. You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, Akbalik G, Wang M et al (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 18(4):603–610. https://doi.org/10.1038/nn.3975

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Liu Z, Ran Y, Tao C, Li S, Chen J, Yang E (2019) Detection of circular RNA expression and related quantitative trait loci in the human dorsolateral prefrontal cortex. Genome Biol 20(1):99. https://doi.org/10.1186/s13059-019-1701-8

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fernández-Chacón R, Königstorfer A, Gerber SH, García J, Matos MF, Stevens CF, Brose N, Rizo J et al (2001) Synaptotagmin I functions as a calcium regulator of release probability. Nature 410(6824):41–49

    Article  PubMed  Google Scholar 

  32. Barbier E, Barchiesi R, Domi A, Chanthongdee K, Domi E, Augier G, Augier E, Xu L et al (2021) Downregulation of synaptotagmin 1 in the prelimbic cortex drives alcohol-associated behaviors in rats. Biol Psychiatry 89(4):398–406. https://doi.org/10.1016/j.biopsych.2020.08.027

    Article  PubMed  CAS  Google Scholar 

  33. Viola TW, Schuch JB, Rovaris DL, Genovese R, Tondo L, Sanvicente-Vieira B, Zaparte A, Cupertino RB et al (2019) Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder. J Neural Transm (Vienna) 126(12):1707–1711. https://doi.org/10.1007/s00702-019-02086-w

    Article  PubMed  CAS  Google Scholar 

  34. Ba W, Selten MM, van der Raadt J, van Veen H, Li LL, Benevento M, Oudakker AR, Lasabuda RSE et al (2016) ARHGAP12 functions as a developmental brake on excitatory synapse function. Cell Rep 14(6):1355–1368. https://doi.org/10.1016/j.celrep.2016.01.037

    Article  PubMed  CAS  Google Scholar 

  35. Williams JT, Christie MJ, Manzoni O (2001) Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 81(1):299–343

    Article  PubMed  CAS  Google Scholar 

  36. Hearing MC, Jedynak J, Ebner SR, Ingebretson A, Asp AJ, Fischer RA, Schmidt C, Larson EB et al (2016) Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement. Proc Natl Acad Sci U S A 113(3):757–762. https://doi.org/10.1073/pnas.1519248113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Agrawal A, Lynskey MT (2009) Candidate genes for cannabis use disorders: findings, challenges and directions. Addiction 104(4):518–532. https://doi.org/10.1111/j.1360-0443.2009.02504.x

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fu R, Tang Y, Li W, Ren Z, Li D, Zheng J, Zuo W, Chen X et al (2021) Endocannabinoid signaling in the lateral habenula regulates pain and alcohol consumption. Transl Psychiatry 11(1):220. https://doi.org/10.1038/s41398-021-01337-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Han W, Li J, Pelkey KA, Pandey S, Chen X, Wang Y-X, Wu K, Ge L et al (2019) Shisa7 is a GABA receptor auxiliary subunit controlling benzodiazepine actions. Science 366(6462):246–250. https://doi.org/10.1126/science.aax5719

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Schmitz LJM, Klaassen RV, Ruiperez-Alonso M, Zamri AE, Stroeder J, Rao-Ruiz P, Lodder JC, van der Loo RJ et al (2017) The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory. Elife 6. https://doi.org/10.7554/eLife.24192

  41. Sabaie H, Talebi M, Gharesouarn J, Asadi MR, Jalaiei A, Arsang-Jang S, Hussen BM, Taheri M et al (2022) Identification and analysis of BCAS4/hsa-miR-185-5p/SHISA7 competing endogenous RNA axis in late-onset Alzheimer’s disease using bioinformatic and experimental approaches. Front Aging Neurosci 14:812169. https://doi.org/10.3389/fnagi.2022.812169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Sabaie H, Gharesouran J, Asadi MR, Farhang S, Ahangar NK, Brand S, Arsang-Jang S, Dastar S et al (2022) Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia. Metab Brain Dis 37(4):1175–1184. https://doi.org/10.1007/s11011-022-00918-5

    Article  PubMed  CAS  Google Scholar 

  43. Jahn R, Scheller RH (2006) SNAREs–engines for membrane fusion. Nat Rev Mol Cell Biol 7(9):631–643

    Article  PubMed  CAS  Google Scholar 

  44. Chen F, Chen H, Chen Y, Wei W, Sun Y, Zhang L, Cui L, Wang Y (2021) Dysfunction of the SNARE complex in neurological and psychiatric disorders. Pharmacol Res 165:105469. https://doi.org/10.1016/j.phrs.2021.105469

    Article  PubMed  CAS  Google Scholar 

  45. Ramos-Miguel A, Beasley CL, Dwork AJ, Mann JJ, Rosoklija G, Barr AM, Honer WG (2015) Increased SNARE protein-protein interactions in orbitofrontal and anterior cingulate cortices in schizophrenia. Biol Psychiatry 78(6):361–373. https://doi.org/10.1016/j.biopsych.2014.12.012

    Article  PubMed  CAS  Google Scholar 

  46. Das J (2020) SNARE complex-associated proteins and alcohol. Alcohol Clin Exp Res 44(1). https://doi.org/10.1111/acer.14238

  47. Neasta J, Barak S, Hamida SB, Ron D (2014) mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse. J Neurochem 130(2):172–184. https://doi.org/10.1111/jnc.12725

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Ucha M, Roura-Martínez D, Ambrosio E, Higuera-Matas A (2020) The role of the mTOR pathway in models of drug-induced reward and the behavioural constituents of addiction. J Psychopharmacol 34(11):1176–1199. https://doi.org/10.1177/0269881120944159

    Article  PubMed  Google Scholar 

  49. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388. https://doi.org/10.1038/nature11993

    Article  PubMed  CAS  Google Scholar 

  50. Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ (2010) Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry 15(12):1176–1189. https://doi.org/10.1038/mp.2009.84

    Article  PubMed  CAS  Google Scholar 

  51. Hollins SL, Zavitsanou K, Walker FR, Cairns MJ (2014) Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure. Transl Psychiatry 4(9):e452. https://doi.org/10.1038/tp.2014.99

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610. https://doi.org/10.1038/nrg2843

    Article  PubMed  CAS  Google Scholar 

  53. Mahmoudi E, Cairns MJ (2017) MiR-137: an important player in neural development and neoplastic transformation. Mol Psychiatry 22(1):44–55. https://doi.org/10.1038/mp.2016.150

    Article  PubMed  CAS  Google Scholar 

  54. Vickstrom CR, Liu X, Liu S, Hu M-M, Mu L, Hu Y, Yu H, Love SL et al (2021) Role of endocannabinoid signaling in a septohabenular pathway in the regulation of anxiety- and depressive-like behavior. Mol Psychiatry 26(7):3178–3191. https://doi.org/10.1038/s41380-020-00905-1

    Article  PubMed  CAS  Google Scholar 

  55. Dever TE, Gutierrez E, Shin B-S (2014) The hypusine-containing translation factor eIF5A. Crit Rev Biochem Mol Biol 49(5):413–425. https://doi.org/10.3109/10409238.2014.939608

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, Marcello GM, Pogatschnigg V et al (2021) Dietary spermidine improves cognitive function. Cell Rep 35(2):108985. https://doi.org/10.1016/j.celrep.2021.108985

    Article  PubMed  CAS  Google Scholar 

  57. Huang Y, Higginson DS, Hester L, Park MH, Snyder SH (2007) Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor. Proc Natl Acad Sci USA 104(10):4194–4199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Kar RK, Hanner AS, Starost MF, Springer D, Mastracci TL, Mirmira RG, Park MH (2021) Neuron-specific ablation of eIF5A or deoxyhypusine synthase leads to impairments in growth, viability, neurodevelopment, and cognitive functions in mice. J Biol Chem 297(5):101333. https://doi.org/10.1016/j.jbc.2021.101333

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Gunasekaran S, Jacob RS, Omkumar RV (2022) Differential expression of miR-148b, miR-129-2 and miR-296 in animal models of schizophrenia-Relevance to NMDA receptor hypofunction. Neuropharmacology 210:109024. https://doi.org/10.1016/j.neuropharm.2022.109024

    Article  PubMed  CAS  Google Scholar 

  60. Ru X, Qu J, Li Q, Zhou J, Huang S, Li W, Zuo S, Chen Y et al (2021) MiR-706 alleviates white matter injury via downregulating PKCα/MST1/NF-κB pathway after subarachnoid hemorrhage in mice. Exp Neurol 341:113688. https://doi.org/10.1016/j.expneurol.2021.113688

    Article  PubMed  CAS  Google Scholar 

  61. Sun Z, Yu J-T, Jiang T, Li M-M, Tan L, Zhang Q, Tan L (2013) Genome-wide microRNA profiling of rat hippocampus after status epilepticus induced by amygdala stimulation identifies modulators of neuronal apoptosis. PLoS ONE 8(10):e78375. https://doi.org/10.1371/journal.pone.0078375

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Zou T, Zhang J, Liu Y, Zhang Y, Sugimoto K, Mei C (2020) Antidepressant-like effect of in mice exposed to a chronic mild stress involves the microRNA-298-5p-mediated Nox1. Front Mol Neurosci 13:131. https://doi.org/10.3389/fnmol.2020.00131

    Article  PubMed  CAS  Google Scholar 

  63. Vallelunga A, Iannitti T, Capece S, Somma G, Russillo MC, Foubert-Samier A, Laurens B, Sibon I et al (2021) Serum miR-96-5P and miR-339-5P are potential biomarkers for multiple system atrophy and Parkinson’s disease. Front Aging Neurosci 13:632891. https://doi.org/10.3389/fnagi.2021.632891

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Dhiraj DK, Chrysanthou E, Mallucci GR, Bushell M (2013) miRNAs-19b, -29b-2* and -339-5p show an early and sustained up-regulation in ischemic models of stroke. PLoS ONE 8(12):e83717. https://doi.org/10.1371/journal.pone.0083717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Long JM, Ray B, Lahiri DK (2014) MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects. J Biol Chem 289(8):5184–5198. https://doi.org/10.1074/jbc.M113.518241

    Article  PubMed  CAS  Google Scholar 

  66. Zou H-Y, Guo L, Zhang B, Chen S, Wu X-R, Liu X-D, Xu X-Y, Li B-Y et al (2022) Aberrant miR-339–5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice. J Clin Invest 132(8). https://doi.org/10.1172/JCI149160

  67. Zhang H, Deng J, Huang K, He Y, Cai Z, He Y (2022) circNup188/miR-760-3p/Map3k8 axis regulates inflammation in cerebral ischemia. Mol Cell Probes 64:101830. https://doi.org/10.1016/j.mcp.2022.101830

    Article  PubMed  CAS  Google Scholar 

  68. Chen D, Lan G, Li R, Mei Y, Shui X, Gu X, Wang L, Zhang T et al (2022) Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer’s disease. Transl Neurodegener 11(1):27. https://doi.org/10.1186/s40035-022-00302-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Massaly N, Dahan L, Baudonnat M, Hovnanian C, Rekik K, Solinas M, David V, Pech S et al (2013) Involvement of protein degradation by the ubiquitin proteasome system in opiate addictive behaviors. Neuropsychopharmacology 38(4):596–604. https://doi.org/10.1038/npp.2012.217

    Article  PubMed  CAS  Google Scholar 

  70. Massaly N, Francès B, Moulédous L (2014) Roles of the ubiquitin proteasome system in the effects of drugs of abuse. Front Mol Neurosci 7:99. https://doi.org/10.3389/fnmol.2014.00099

    Article  PubMed  Google Scholar 

  71. Werner CT, Viswanathan R, Martin JA, Gobira PH, Mitra S, Thomas SA, Wang Z-J, Liu J-F et al (2018) E3 ubiquitin-protein ligase SMURF1 in the nucleus accumbens mediates cocaine seeking. Biol Psychiatry 84(12):881–892. https://doi.org/10.1016/j.biopsych.2018.07.013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Zhou Y, Ge Y, Liu Q, Li Y-X, Chao X, Guan J-J, Diwu Y-C, Zhang Q (2021) LncRNA BACE1-AS promotes autophagy-mediated neuronal damage through the miR-214-3p/ATG5 signalling axis in Alzheimer’s disease. Neuroscience 455:52–64. https://doi.org/10.1016/j.neuroscience.2020.10.028

    Article  PubMed  CAS  Google Scholar 

  73. Irie K, Tsujimura K, Nakashima H, Nakashima K (2016) MicroRNA-214 promotes dendritic development by targeting the schizophrenia-associated gene quaking (Qki). J Biol Chem 291(26):13891–13904. https://doi.org/10.1074/jbc.M115.705749

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Zhang M, Zhou H, He R, Yang J, Zou Y, Deng Y, Xie H, Yan Z (2022) Up-regulating microRNA-214-3p relieves hypoxic-ischemic brain damage through inhibiting TXNIP expression. Mol Cell Biochem. https://doi.org/10.1007/s11010-022-04530-0

    Article  PubMed  PubMed Central  Google Scholar 

  75. Chavoshi H, Boroujeni ME, Abdollahifar M-A, Amini A, Tehrani AM, Moghaddam MH, Norozian M, Farahani RM et al (2020) From dysregulated microRNAs to structural alterations in the striatal region of METH-injected rats. J Chem Neuroanat 109:101854. https://doi.org/10.1016/j.jchemneu.2020.101854

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This research was supported by the National Natural Science Foundation of China (81971792, and 81901920) and the Fundamental Research Funds for the Central Universities.

Author information

Authors and Affiliations

  1. College of Forensic Medicine, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China

    Xixi Yang, Dongyu Yu, Feifei Gao, Jingsi Yang, Zhennan Chen, Junlin Liu, Xiaoyu Yang, Lanjiang Li, Yuxiang Zhang & Chunxia Yan

  2. Key Laboratory of Forensic Medicine, National Health Commission, Xi’an 710061, Shaanxi, China

    Xixi Yang, Dongyu Yu, Feifei Gao, Jingsi Yang, Zhennan Chen, Junlin Liu, Xiaoyu Yang, Lanjiang Li, Yuxiang Zhang & Chunxia Yan

  3. Bio-Evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi’an Jiaotong University, Xi’an 710100, Shaanxi, China

    Xixi Yang, Dongyu Yu, Feifei Gao, Jingsi Yang, Zhennan Chen, Junlin Liu, Xiaoyu Yang, Lanjiang Li, Yuxiang Zhang & Chunxia Yan

Authors
  1. Xixi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dongyu Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feifei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jingsi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhennan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junlin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoyu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lanjiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuxiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chunxia Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CXY and YXZ designed the study. XXY performed the experiment and bioinformatics analysis. DYY, FFG, JSY and ZNC analysed the data. JLL, XYY and LJL checked the data. XXY wrote the manuscript. CXY and YXZ revised the manuscript. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Yuxiang Zhang or Chunxia Yan.

Ethics declarations

Ethics Approval

Animal experiments were approved ethically by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University (No. 2022–1174).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, X., Yu, D., Gao, F. et al. Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03859-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-023-03859-x

Keywords

Search

Navigation