Şizofrenide Güncel Translasyonel Tıp Yaklaşımı Olarak MikroRNA Araştırmaları

Year 2025, Volume: 17 Issue: 2, 283 - 300

Ceren Gümüş , Fatih Atilla Bağcı , Esra Boztepe , Emine Merve Akdağ , Dilek Pirim

https://doi.org/10.18863/pgy.1428012

Abstract

Şizofreni toplum sağlığını önemli ölçüde etkileyen semptomlarla seyreden yaygın ve kompleks bir psikiyatrik hastalıktır. Aday gen çalışmalarında şizofreni ile ilişkili glutamaterjik, dopaminerjik ve GABAerjik sinyal yolakları gibi moleküler yolaklarda etkin genlerde bulunan varyantların şizofreni riskini arttırdığı raporlanmıştır. Ancak, araştırmaların spesifik popülasyonlarda sınırlı sayılı örnek grupları ile sınırlı olması sebebiyle şu ana kadar elde edilen veriler translasyonel tıp alanında yeni yaklaşımların geliştirilmesi için eksik kalmaktadır. Moleküler düzeyde yapılan araştırmaların sonuçları umut verici olsa da hastalık yönetimi için gerekli erken tanı ve tedavi yöntemleri yetersizdir ve bu yönde daha fazla araştırma yapılmasına ihtiyaç duyulmaktadır. Son yıllarda yapılan çalışmalarda postmortem beyin dokusunda ve vücut sıvılarında tespit edilen bazı mikroRNA’ların şizofreni hastaları ve kontrol gruplarında farklı eksprese olarak şizofreni etiyolojisi ile ilişkili olabilecekleri raporlanmıştır. Şizofreni patofizyolojisi ile ilişkili mikroRNA profillerinin belirlenmesi hastalığın erken tanı ve tedavisinde yeni moleküler yaklaşımların geliştirilmesi açısından oldukça önemli olsa da literatürde bu alanda boşluklar vardır. Mevcut literatürde şizofreni ile ilişkili mikroRNA’ları raporlayan çalışmalar metodolojik olarak farklılıklar içermektedir. Son on yılda şizofreni ve mikroRNA ilişkisini araştıran araştırmaların incelendiği bu derleme, özellikle örnek seçiminin ve mikroRNA tespit yöntemlerinin çalışmalarda uyumlu sonuçların alınması açısından oldukça önemli olduğunu ortaya koymuştur. Postmortem beyin dokusunda eksprese olan mikroRNA’ların minimal invaziv olarak vücut sıvılarından tespiti şizofreni yönetimi için umut verici sonuçlar doğurabilir. Bu kapsamda yaptığımız kapsamlı literatür araştırması sonrası miR-124-3p, miR-16-5p ve miR-34a-5p şizofreni için potansiyel epigenetik biyobelirteç olarak önceliklendirilmiş ve mikroRNA’ların hastalığın toplumdaki yükünün hafifletilmesi için geliştirilecek translasyonel tıp yaklaşımlarında kullanım potansiyeli üzerine veri sunulmuştur.

Keywords

Şizofreni, mikroRNA, epigenetik, biyobelirteç, translasyonel tıp

Current Translational Medicine Approach in Schizophrenia: MicroRNA Research

Abstract

Schizophrenia is a common and complex psychiatric disorder with symptoms that significantly affect public health. Candidate gene studies reported that variants in genes involved in molecular processes associated with schizophrenia such as glutamatergic, dopaminergic, and GABAergic signaling pathways increase the risk of schizophrenia. Yet, the data obtained so far are incomplete for the development of new translational medicine approaches. Although the current research has promising results, it is still insufficient for the development of early diagnosis and treatment methods for schizophrenia management. Recent studies have reported that microRNAs detected in brain tissue and body fluids are differentially expressed in schizophrenia patients and control groups may be related to the etiology of schizophrenia. Although the determination of microRNA profiles associated with schizophrenia pathophysiology is very important for the development of new molecular approaches in the early diagnosis and treatment of the disease, the literature is still lacking in this field. Studies reporting schizophrenia-associated microRNAs in the existing literature have some limitations and methodological differences. In this review, we extracted the studies investigating the relationship between schizophrenia and microRNA in the last ten years and it was revealed that sample selection and microRNA detection methods are very important in terms of obtaining consistent results. Non-invasive detection of microRNAs expressed in the brain may have promising results for schizophrenia management. In this context, after a comprehensive literature search, miR-124-3p, miR-16-5p, and miR-34a-5p, which are differentially expressed in schizophrenia patients in the brain and blood, were prioritized as potential epigenetic biomarkers for schizophrenia. Our study provides data that can be utilized for translational medicine approaches to alleviate the burden of the disease in the community.

Keywords

Schizophrenia, microRNA, epigenetic, biomarker, translational medicine

References

• Alacam H, Akgun S, Akca H, Ozturk O, Kabukcu BB, Herken H (2016) miR-181b-5p, miR-195-5p and miR-301a-3p are related with treatment resistance in schizophrenia. Psychiat Res, 245:200–206.
• Ambrozová L, Zeman T, Janout V, Janoutová J, Lochman J, Šerý O (2023) Association between polymorphism rs2421943 of the insulin‐degrading enzyme and schizophrenia: Preliminary report. J Clin Lab Anal, 37:e24949.
• Amoah SK, Rodriguez BA, Logothetis CN, Chander P, Sellgren CM, Weick JP et al. (2020) Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics. Neuropsychopharmacology, 45:656–665.
• Asadi MR, Gharesouran J, Sabaie H, Moslehian MS, Dehghani H, Arsang-Jang S et al. (2022) Assessing the expression of two post-transcriptional BDNF regulators, TTP and miR-16 in the peripheral blood of patients with schizophrenia. BMC Psychiatry, 22:771.
• Ayari F, Chaaben AB, Abaza H, Mihoub O, Ouni N, Boukouaci W et al. (2024) Association between genetic variants of TLR2, TLR4, TLR9 and schizophrenia. Encephale, 50:178-184.
• Bai J, Shi Z, Wang S, Pan H, Zhang T (2022) MiR-21 and let-7 cooperation in the regulation of lung cancer. Front Oncol, 12:950043
• Balasubramanian R, Vinod PK (2022) Inferring miRNA sponge modules across major neuropsychiatric disorders. Front Mol Neurosci, 15:1009662.
• Bashir AO, El-Mesery ME, Anwer R, Eissa LA (2020) Thymoquinone potentiates miR-16 and miR-375 expressions in hepatocellular carcinoma. Life Sci, 254:117794.
• Birdi A, Kumar PK, Nebhinani N, Gupta T, Tomo S, Purohit P et al. (2023) Association of circulatory klotho levels and its expression with miRNA- 339 in patients with schizophrenia. Behav Brain Res, 445:114359.
• Bradshaw NJ, Ukkola-Vuoti L, Pankakoski M, Zheutlin AB, Ortega-Alonso A, Torniainen-Holm M et al. (2017) The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484. Open Biol, 7:170153.
• Brum CB, Paixão-Côrtes VR, Carvalho AM, Martins-Silva T, Carpena MX, Ulguim KF et al. (2021) Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility. World J Biol Psychiatry, 22:456–467.
• Cao H, Baranova A, Yue W, Yu H, Zhu Z, Zhang F et al. (2020) miRNA-coordinated schizophrenia risk network cross-talk with cardiovascular repair and opposed gliomagenesis. Front Genet, 11:149.
• Cao JY, Wang B, Tang TT, Wen Y, Li ZL, Feng ST et al. (2021) Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury. Theranostics, 11:5248–5266.
• Cattane N, Mora C, Lopizzo N, Borsini A, Maj C, Pedrini L et al. (2019) Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: new insights for the key role of miR-125b-1-3p in neurodevelopmental processes. Schizophr Res, 205:63–75.
• Chen BY, Lin JJ, Lu MK, Tan HP, Jang FL, Lin SH (2021a) Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia. NPJ Schizophr, 7:35.
• Chen C, Meng Q, Xia Y, Ding C, Wang L, Dai R et al. (2018) POU3F2 is a regulator of a gene coexpression network in brain tissue from patients with neuropsychiatric disorders. Sci Transl Med, 10:eaat8178.
• Chen ML, Hong CG, Yue T, Li HM, Duan R, Hu WB et al. (2021b) Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer’s disease by enhancing autophagy. Theranostics, 11:2395–2409.
• Chen S, Sun X, Niu W, Kong L, He M, Fan H et al. (2016) A preliminary analysis of microRNA-21 expression alteration after antipsychotic treatment in patients with schizophrenia. Psychiatry Res, 244:324–332.
• Cheng LC, Pastrana E, Tavazoie M, Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci, 12:399–408.
• Davarinejad O, Najafi S, Zhaleh H, Golmohammadi F, Radmehr F, Alikhani M et al. (2022) MiR-574-5P, miR-1827, and miR-4429 as potential biomarkers for schizophrenia. J Mol Neurosci, 72:226–238.
• Ding Z, Liu SJ, Liu XW, Ma Q, Qıao Z (2020) MiR-16 inhibits proliferation of cervical cancer cells by regulating KRAS. Eur Rev Med Pharmacol Sci, 24:10419–10425.
• Du Y, Yu Y, Hu Y, Li X-W, Wei Z-X, Pan R-Y et al. (2019) Genome-wide, integrative analysis implicates exosome-derived microRNA dysregulation in schizophrenia. Schizophr Bull, 45:1257–1266.
• Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T rt al. (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res, 43:W460–W466.
• Fan H, Sun X, Niu W, Zhao L, Zhang QL, Li W et al. (2015) Altered microRNA expression in peripheral blood mononuclear cells from young patients with schizophrenia. J Mol Neurosci, 56:562–571.
• Fang S, Wang T, Weng L, Han X, Zheng R, Zhang H (2023) Lung cancer-derived exosomal miR-132-3p contributed to interstitial lung disease development. World J Surg Oncol, 21:205.
• Fu X, Liu Y, Baranova A, Zhang F (2022) Deregulatory miRNA-BDNF network inferred from dynamic expression changes in schizophrenia. Brain Sci, 12:167.
• Funahashi Y, Yoshino Y, Iga J, Ueno S (2023) Impact of clozapine on the expression of miR-675-3p in plasma exosomes derived from patients with schizophrenia. World J Biol Psychiatry, 24:303–313.
• Gallego J, Alsop E, Lencz T, Van Keuren-Jensen K, Malhotra A. (2018) F10. Differential expression of microRNAs in cerebrospinal fluid and plasma samples in schizophrenia. Schizophr Bull, 44:S221–2.
• Geaghan MP, Atkins JR, Brichta AM, Tooney PA, Scott RJ, Carr VJ et al. (2019) Alteration of miRNA-mRNA interactions in lymphocytes of individuals with schizophrenia. J Psychiatr Res,112:89–98.
• Goldie BJ, Dun MD, Lin M, Smith ND, Verrills NM, Dayas CV et al. (2014) Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons. Nucleic Acids Res, 42:9195–9208.
• Gou M Pan S, Tong J, Zhou Y, Han J, Xie T et al. (2021) Effects of microRNA-181b-5p on cognitive deficits in first-episode patients with schizophrenia: Mediated by BCL-2. J Psychiatr Res, 136:358–365.
• Grosu ȘA, Dobre M, Milanesi E, Hinescu ME (2023) Blood-based microRNAs in psychotic disorders—a systematic review. Biomedicines, 11:2536.
• Gu J, Xu H, Chen Y, Li N, Hou X (2022) MiR-223 as a regulator and therapeutic target in liver diseases. Front Immunol, 13:860661 .
• Gui Y, Wang L, Huang Z (2021) MiR-137 inhibits cervical cancer progression via down-modulating Notch1 and inhibiting the PI3K/AKT/mTOR signaling pathway. Transl Cancer Res, 10:3748–3756.
• Guo X, Yang J, Huang J, Chen Z, Wu X, Zhu L et al. (2019) Influence of CTNNB1 rs2953 polymorphism on schizophrenia susceptibility in Chinese Han population through modifying miR-485 binding to CTNNB1. Genes Brain Behav, 18:e12524.
• Han S, Li Y, Gao J (2023) Peripheral blood microRNAs as biomarkers of schizophrenia: expectations from a meta-analysis that combines deep learning methods. World J Biol Psychiatry, 25:65–81.
• Hart M, Diener C, Lunkes L, Rheinheimer S, Krammes L, Keller A et al. (2023) miR-34a-5p as molecular hub of pathomechanisms in Huntington’s disease. Mol Med, 29:43.
• He K, Guo C, Guo M, Tong S, Zhang Q, Sun H et al. (2019) Identification of serum microRNAs as diagnostic biomarkers for schizophrenia. Hereditas, 156:23.
• Henriques DG, Miranda RL, Dezonne RS, Wildemberg LE, Camacho AH da S, Chimelli L et al. (2023) miR-383-5p, miR-181a-5p, and miR-181b-5p as predictors of response to first-generation somatostatin receptor ligands in acromegaly. Int J Mol Sci, 24:2875.
• Holland A, Enrick M, Diaz A, Yin L (2023) Is miR-21 a therapeutic target in cardiovascular disease? Int J Drug Discov Pharm, 2:26–36.
• Horai T, Boku S, Okazaki S, Otsuka I, Ratta-apha W, Mouri K et al. (2020) miR-19b is elevated in peripheral blood of schizophrenic patients and attenuates proliferation of hippocampal neural progenitor cells. J Psychiatr Res, 131:102–107.
• Hu Z, Gao S, Lindberg D, Panja D, Wakabayashi Y, Li K et al. (2019) Temporal dynamics of miRNAs in human DLPFC and its association with miRNA dysregulation in schizophrenia. Transl Psychiatry, 9:196.
• Huang C-K, Bär C, Thum T (2020a) miR-21, mediator, and potential therapeutic target in the cardiorenal syndrome. Front Pharmacol, 11:726.
• Huang H, Luo J, Qi Y, Wu Y, Qi J, Yan X et al. (2023) Comprehensive analysis of circRNA expression profile and circRNA-miRNA-mRNA network susceptibility to very early-onset schizophrenia. Schizophrenia (Heidelb), 9:70.
• Huang X, Bao C, Lv Q, Zhao J, Wang Y, Lang X et al. (2020b) Sex difference in cognitive impairment in drug-free schizophrenia: association with miR-195 levels. Psychoneuroendocrinology, 119:104748.
• Ibrahim RR, Amer RA, Abozeid AA, Elsharaby RM, Shafik NM (2020) Micro RNA 146a gene variant / TNF-α / IL-6 / IL-1 β; A cross-link axis inbetween oxidative stress, endothelial dysfunction and neuro-inflammation in acute ischemic stroke and chronic schizophrenic patients. Arch Biochem Biophys, 679:108193.
• Jafri I, Alsharif G, Bland GN, Gambhir KK (2019). Erythrocyte miRNA 144 and miRNA 451 as cell aging biomarkers in African American adults. Open Biochem J, 13:81-87.
• Janoutová J, Janácková P, Serý O, Zeman T, Ambroz P, Kovalová M et al. (2016) Epidemiology and risk factors of schizophrenia. Neuro Endocrinol Lett, 37:1–8.
• Jiang T, Cheng H (2021) miR-34a-5p blocks cervical cancer growth and migration by downregulating CDC25A. J BUON, 26:1768–1774.
• Jin M, Liu Y, Hu G, Li X, Jia N, Cui X et al. (2023) Establishment of a schizophrenia classifier based on peripheral blood signatures and investigation of pathogenic miRNA-mRNA regulation. J Psychiatr Res, 159:172–184.
• Jin M, Zhu X, Sun Y, Li Z, Li X, Ai L et al. (2022) Identification of peripheral blood miRNA biomarkers in first-episode drug-free schizophrenia patients using bioinformatics strategy. Mol Neurobiol, 59:4730–4746.
• Johnstone AL, O’Reilly JJ, Patel AJ, Guo Z, Andrade NS, Magistri M et al. (2018) EZH1 is an antipsychotic-sensitive epigenetic modulator of social and motivational behavior that is dysregulated in schizophrenia. Neurobiol Dis, 119:149–158.
• Kato H, Kimura H, Kushima I, Takahashi N, Aleksic B, Ozaki N (2023) The genetic architecture of schizophrenia: review of large-scale genetic studies. J Hum Genet, 68:175–182.
• Khadimallah I, Jenni R, Cabungcal J-H, Cleusix M, Fournier M, Beard E et al. (2022) Mitochondrial, exosomal miR137-COX6A2 and gamma synchrony as biomarkers of parvalbumin interneurons, psychopathology, and neurocognition in schizophrenia. Mol Psychiatry, 27:1192–1204.
• Kimoto S, Glausier JR, Fish KN, Volk DW, Bazmi HH, Arion D et al. (2016) reciprocal alterations in regulator of g protein signaling 4 and microRNA16 in schizophrenia. Schizophr Bull, 42:396–405.
• Lai C-Y, Lee S-Y, Scarr E, Yu YH, Lin YT, Liu CM et al. (2016) Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue. Transl Psychiatry, 6:e717.
• Li B, Tao Q, Hu X, Li T, Bao Y (2023a) miR-181b-5p promotes cell proliferation and induces apoptosis in human acute myeloid leukemia by targeting PAX9. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 39:1074–1082.
• Li C, Han S, Zhu J, Cheng F (2023b) MiR-132-3p activation aggravates renal ischemia-reperfusion injury by targeting Sirt1/PGC1alpha axis. Cell Signal, 110:110801.
• Li J, Chen H, Sun G, Zhang X, Ye H, Wang P (2023c) Role of miR-21 in the diagnosis of colorectal cancer: Meta-analysis and bioinformatics. Pathol Res Pract, 248, 154670.
• Li R, Wang Q, Qiu Y, Meng Y, Wei L, Wang H et al. (2021) A potential autophagy-related competing endogenous RNA network and corresponding diagnostic efficacy in schizophrenia. Front Psychiatry, 12:628361.
• Lim M, Carollo A, Neoh MJY, Esposito G (2023) Mapping miRNA research in schizophrenia: a scientometric review. Int J Mol Sci, 24:436.
• Liu D, Wu L, Wei H, Zhu C, Tian R, Zhu W et al. (2022) The SFT2D2 gene is associated with the autoimmune pathology of schizophrenia in a Chinese population. Front Neurol, 13:1037777.
• Liu S, Zhang F, Shugart YY, Yang L, Li X, Liu Z et al. (2017a) The early growth response protein 1-miR-30a-5p-neurogenic differentiation factor 1 axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring. Transl Psychiatry, 7:e998.
• Liu S, Zhang F, Wang X, Shugart YY, Zhao Y, Li X et al. (2017b) Diagnostic value of blood-derived microRNAs for schizophrenia: results of a meta-analysis and validation. Sci Rep, 7:15328.
• Lobentanzer S, Hanin G, Klein J, Soreq H (2019) Integrative transcriptomics reveals sexually dimorphic control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder. Cell Rep, 29:764.e5-777.e5.
• Long J, Tian L, Baranova A, Cao H, Yao Y, Rao S et al. (2022) Convergent lines of evidence supporting involvement of NFKB1 in schizophrenia. Psychiatry Res, 312:114588.
• Luo L, Sun L, Li S, Liu H, Chen Z, Huang S et al. (2024) miR-124-3p regulates the involvement of Ptpn1 in testicular development and spermatogenesis in mouse. Gene, 893:147967.
• Luo Y, Hu S, Wang F, Yang J, Gong D, Xu W et al. (2022) miR-137 represses migration and cell motility by targeting COX-2 in non-small cell lung cancer. Transl Cancer Res, 11:3803-3813.
• Lv J, Zhao HP, Dai K, Cheng Y, Zhang J, Guo L (2020) Circulating exosomal miRNAs as potential biomarkers for Barrett's esophagus and esophageal adenocarcinoma. World J Gastroenterol, 26:2889-2901.
• Lv S, Liu L, Yang B, Zhao X (2022) Association of miR-9-5p and NFIC in the progression of gastric cancer. Hum Exp Toxicol, 41:09603271221084671.
• Lv Y, Xie X, Zou G, Kong M, Yang J, Chen J et al. (2023) miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma. Precis Clin Med, 6:pbad027.
• Ma J, Shang S, Wang J, Zhang T, Nie F, Song X et al. (2018) Identification of miR-22-3p, miR-92a-3p, and miR-137 in peripheral blood as biomarker for schizophrenia. Psychiatry Res, 265:70–76.
• Maekawa M, Yamada K, Toyoshima M, Ohnishi T, Iwayama Y, Shimamoto C et al. (2015) Utility of scalp hair follicles as a novel source of biomarker genes for psychiatric illnesses. Biol Psychiatry, 78:116–125.
• Martins H C, Schratt G (2021) MicroRNA-dependent control of neuroplasticity in affective disorders. Transl Psychiatry, 11:263.
• Morozova A, Zorkina Y, Pavlov K, Pavlova O, Abramova O, Ushakova V et al. (2021) Associations of genetic polymorphisms and neuroimmune markers with some parameters of frontal lobe dysfunction in schizophrenia. Front Psychiatry, 12:655178.
• Namkung H, Yukitake H, Fukudome D, Lee BJ, Tian M, Ursini G et al. (2023) The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder. Neuron, 111:220-235.e9
• Nomair AM, Mekky JF, El-hamshary SA, Nomeir HM (2023) Circulating miR-146a-5p and miR-132–3p as potential diagnostic biomarkers in epilepsy. Epilepsy Res, 191:107089.
• Pala E, Denkçeken T (2020) Evaluation of miRNA expression profiles in schizophrenia using principal-component analysis-based unsupervised feature extraction method. J Comput Biol, 27:1253–1263.
• Pan S, Feng W, Li Y, Huang J, Chen S, Cui Y et al. (2021) The microRNA-195 - BDNF pathway and cognitive deficits in schizophrenia patients with minimal antipsychotic medication exposure. Transl Psychiatry, 11:117.
• Panja D, Li Y, Ward ME, Li Z (2021) miR-936 is increased in schizophrenia and inhibits neural development and AMPA receptor-mediated synaptic transmission. Schizophr Bull, 47:1795–1805.
• Peng Q, Dai Z, Yin J, Lv D, Luo X, Xiong S et al. (2023) Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients. Front Psychiatry, 14:1187111.
• Peng R, Cao J, Su B-B, Bai X-S, Jin X, Wang A-Q et al. (2022) Down-regulation of circPTTG1IP induces hepatocellular carcinoma development via miR-16-5p/RNF125/JAK1 axis. Cancer Lett, 543:215778.
• Pergola G, Rampino A, Sportelli L, Borcuk CJ, Passiatore R, Di Carlo P et al. (2023) A miR-137-related biological pathway of risk for schizophrenia is associated with human brain emotion processing. Biol Psychiatry Cogn Neurosci Neuroimaging, 9:356-366.
• Roy B, Yoshino Y, Allen L, Prall K, Schell G, Dwivedi Y (2020) Exploiting circulating microRNAs as biomarkers in psychiatric disorders. Mol Diagn Ther, 24:279–298.
• Sabaie H, Gharesouran J, Asadi MR, Farhang S, Ahangar NK, Brand S et al. (2022a) Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia. Metab Brain Dis, 37:1175–1184.
• Sabaie H, Gholipour M, Asadi MR, Abed S, Sharifi-Bonab M, Taheri M ett al. (2022b) Identification of key long non-coding RNA-associated competing endogenous RNA axes in Brodmann Area 10 brain region of schizophrenia patients. Front Psychiatry, 13:1010977.
• Sabaie H, Mazaheri Moghaddam M, Mazaheri Moghaddam M, Amirinejad N, Asadi MR, Daneshmandpour Y et al. (2021a) Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis. Sci Rep, 11:24497.
• Sabaie H, Moghaddam MM, Moghaddam MM, Ahangar NK, Asadi MR, Hussen BM et al. (2021b) Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia. Sci Rep, 11:24413.
• Schlichtholz, L (2022) The role of miR-16 in embryonic brain development (Doctoral thesis). Johannes Gutenberg-Universität Mainz.
• Shafiee-Kandjani AR, Nezhadettehad N, Farhang S, Bruggeman R, Shanebandi D, Hassanzadeh M et al. (2023) MicroRNAs and pro-inflammatory cytokines as candidate biomarkers for recent-onset psychosis. BMC Psychiatry, 23:631.
• Smalheiser NR, Lugli G, Zhang H, Rizavi H, Cook EH, Dwivedi Y (2014) Expression of microRNAs and other small rnas in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects. PLoS One, 9:e86469.
• Song H, Sun X, Zhang L, Zhao L, Guo Z, Fan H et al. (2014) A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment. J Psychiatr Res, 54:134–140.
• Sotelo-Ramírez CE, Camarena B, Sanabrais-Jiménez MA, Zaragoza-Hoyos JU, Ordoñez-Martínez B, Escamilla-Orozco RI et al. (2023) Toll-Like Receptor (TLR) 1, 2, and 6 gene polymorphisms support evidence of innate immune factors in schizophrenia. Neuropsychiatr Dis Treat, 19:2353–2361.
• Sözen MM, Kartalcı Ş (2023) Association of a haplotype in the NRG1 gene with schizophrenia: a case-control study. Turk J Biochem, 48:246–256.
• Stilo SA, Murray RM (2019) Non-Genetic factors in schizophrenia. Curr Psychiatry Rep, 21:100.
• Sun Q, Zhao Y, Zhang K, Su H, Chen T, Jiang H et al. (2020) An association study between methamphetamine use disorder with psychosis and polymorphisms in MiRNA. Neurosci Lett, 717:134725.
• Sun X, Lu J, Zhang L, Song H, Zhao L, Fan H et al. (2015) Aberrant microRNA expression in peripheral plasma and mononuclear cells as specific blood-based biomarkers in schizophrenia patients. J Clin Neurosci, 22:570–574.
• Thomas KT, Zakharenko SS (2021) MicroRNAs in the onset of schizophrenia. Cells, 10:2679.
• Tian H, Zhao Y, Du C, Zong X, Zhang X, Qiao X (2021) Expression of miR-210, miR-137, and miR-153 in patients with acute cerebral infarction. Biomed Res Int, 2021:4464945.
• Tsoporis JN, Ektesabi AM, Gupta S, Izhar S, Salpeas V, Rizos IK et al. (2022) A longitudinal study of alterations of circulating DJ-1 and miR203a-3p in association to olanzapine medication in a sample of first episode patients with schizophrenia. J Psychiatr Res, 146:109–117.
• Wang Y, Fang J, Gu F (2022) MiR-125b-5p/TPD52 axis affects proliferation, migration and invasion of breast cancer cells. Mol Biotechnol, 64:1003–1012.
• Wang Y, Wang J, Guo T, Peng Y, Wang K, Bai K et al. (2019) Screening of schizophrenia associated miRNAs and the regulation of miR-320a-3p on integrin β1. Medicine (Baltimore), 98:e14332.
• Wang Z, Hu S, Li X, Liu Z, Han D, Wang Y et al. (2021) MiR-16-5p suppresses breast cancer proliferation by targeting ANLN. BMC Cancer, 21:1188.
• Wen D, Zhang H, Zhou Y, Wang J (2022a) The molecular mechanisms and function of miR-15a/16 dysregulation in fibrotic diseases. Int J Mol Sci, 23:16041.
• Wen Y, Huang H, Huang B, Liao X (2022b) HSA-miR-34a-5p regulates the SIRT1/TP53 axis in prostate cancer. Am J Transl Res, 14:4493–4504.
• Wu S, Wang P, Tao R, Yang P, Yu X, Li Y et al. (2020) Schizophrenia-associated microRNA-148b-3p regulates COMT and PRSS16 expression by targeting the ZNF804A gene in human neuroblastoma cells. Mol Med Rep, 22:1429–1439.
• Xie M, Li Z, Li X, Ai L, Jin M, Jia N et al. (2022) Identifying crucial biomarkers in peripheral blood of schizophrenia and screening therapeutic agents by comprehensive bioinformatics analysis. J Psychiatr Res, 152:86–96.
• Xu Y, Yue W, Yao Shugart Y, Li S, Cai L, Li Q et al. (2016) Exploring transcription factors-microRNAs co-regulation networks in schizophrenia. Schizophr Bull, 42:1037–1045.
• Yao W, Zhou P, Yan Q, Wu X, Xia Y, Li W et al. (2023) ERVWE1 reduces hippocampal neuron density and impairs dendritic spine morphology through inhibiting Wnt/JNK non-canonical pathway via miR-141-3p in schizophrenia. Viruses, 15:168.
• Ying S, Heung T, Zhang Z, Yuen RKC, Bassett AS (2022) Schizophrenia risk mediated by microRNA target genes overlapped by genome-wide rare copy number variation in 22q11.2 deletion syndrome. Front Genet, 13:812183.
• You X, Zhang Y, Long Q, Liu Z, Ma X, Lu Z et al. (2020) Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment-resistant schizophrenia using miRNA sequencing and integrated bioinformatics. Mol Med Rep, 22:4340–4350.
• Yu H, Wu J, Zhang H, Zhang G, Sui J, Tong W et al. (2015) Alterations of miR-132 are novel diagnostic biomarkers in peripheral blood of schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry, 63:23–29.
• Yuan S, Wu Q, Wang Z, Che Y, Zheng S, Chen Y et al. (2021) miR-223: an immune regulator in infectious disorders. Front Immunol, 12:781815.
• Zanjirband M, Rahgozar S, Aberuyi N (2023) miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression (WIP1) in childhood acute lymphoblastic leukemia. Cancer Drug Resist, 6:242–256.
• Zhang C-Y, Xiao X, Zhang Z, Hu Z, Li M (2022) An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data. Mol Psychiatry, 27:95–112.
• Zhang H-C, Du Y, Chen L, Yuan Z-Q, Cheng Y (2023) MicroRNA schizophrenia: etiology, biomarkers and therapeutic targets. Neurosci Biobehav Rev, 146, 105064.
• Zhang M-W, Shen Y-J, Shi J, Yu J-G (2021) MiR-223-3p in cardiovascular diseases: a biomarker and potential therapeutic target. Front Cardiovasc Med, 7:610561.
• Zhang WH, Jiang L, Li M, Liu J (2023) MicroRNA 124: An emerging therapeutic target in central nervous system disorders. Exp Brain Res, 241:1215–1226.
• Zhao X, Liu Y, Long Q, Zhang Y, You X, Guo Z et al. (2023) Abnormal expression of miR-3653-3p, caspase 1, IL-1β in peripheral blood of schizophrenia. BMC Psychiatry, 23:822.
• Zhao Z, Jinde S, Koike S, Tada M, Satomura Y, Yoshikawa A et al. (2019) Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes. Transl Psychiatry, 9:289.
• Zhou L, Chen D, Liu P, Chen L, Su Y (2022) miR-132-3p participates in the pathological mechanism of temporomandibular joint osteoarthritis by targeting PTEN. Arch Oral Biol, 142:105511.
• Zhu K, Lin J, Chen S, Xu Q (2021) miR-9-5p promotes lung adenocarcinoma cell proliferation, migration and invasion by targeting ID4. Technol Cancer Res Treat, 20:15330338211048592.
• Zhu X, He L, Li X, Pei W, Yang H, Zhong M et al. (2023) LncRNA AK089514/miR-125b-5p/TRAF6 axis mediates macrophage polarization in allergic asthma. BMC Pulm Med, 23:45.