{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T18:23:00Z","timestamp":1757614980155,"version":"3.44.0"},"reference-count":30,"publisher":"Centre for Evaluation in Education and Science (CEON\/CEES)","issue":"6","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/BY\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Biochemistry"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>Background: To investigate the mechanism of miR-4465 targeting PTEN-mediated autophagy of astrocytes in epilepsy. Methods: Serum samples were collected from epileptic children and healthy children. Extract foreign bodies from serum samples and determine their quality. The exosomes were sequenced, and the abnormal expression of miRNA in patients' serum exosomes was analysed, and the expression of miR-4465 was verified by quantitative PCR. Bioinformatics predicts the size of miR-4465 and makes GO and KEGG analyses. HEK293 cells were cultured, and the relationship between miR-4465 and its target was detected using the double luciferase reporting method. Astrocytes were cultured, and quantitative PCR and WB were used to detect the expression of miR-4465 and PTEN after overexpression. In addition, CCK-8 and WB were used to detect the growth of miR-4465 and the changes of autophagy-related proteins ATG5 and Beclin1, respectively. Results: miR-4465 was markedly increased in exosomes. The bioinformatic analysis found the differentially expressed target genes of miR-4465 were mainly enriched in molecular binding, molecular function regulation, and other molecular functions and participated in cell adhesion, cell-extracellular matrix receptor interaction, and the Rap1 signalling pathway. PTEN has been predicted as a target gene of miR-4465; meanwhile, the results of the dual-luciferase reporter assay confirmed the interaction between miR-4465 and PTEN. Quantitative PCR, as well as WB results, suggested the level of PTEN was decreased in serum exosomes of patients with epilepsy, while increased miR-4465 expression inhibited expressions of PTEN. CCK-8, as well as WB results, suggested miR-4465 could suppress the growth of astrocytes and promote ATG5 as well as Beclin1 expression; finally, up-regulation of PTEN partially alleviated effects of miR-4465 on astrocytes growth as well as autophagy. Conclusions: In children with epilepsy, miR-4465 can target and regulate PTEN to promote autophagy in astrocytes.<\/jats:p>","DOI":"10.5937\/jomb0-52626","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:23:12Z","timestamp":1744777392000},"page":"1347-1356","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of miR-4465 targeting PTEN-mediated autophagy of astrocytes in epilepsy"],"prefix":"10.5937","volume":"44","author":[{"given":"Jinhua","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3964","reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Fine A, Wirrell EC: Seizures in Children. Pediatr Rev 2020; 41(7): 321-47.;","DOI":"10.1542\/pir.2019-0134"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Song P , Liu Y , Yu X, Wu J, Poon AN, Demaio A, Wang W , Rudan I, Chan KY: Prevalence of epilepsy in China between 1990 and 2015: A systematic review and meta-analysis. J Glob Health 2017; 7(2): 020706.;","DOI":"10.7189\/jogh.07.020706"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Guerrini R: Epilepsy in children. Lancet 2006; 367(9509): 499-524.;","DOI":"10.1016\/S0140-6736(06)68182-8"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Thijs RD, Surges R, O'Brien TJ, Sander JW: Epilepsy in adults. Lancet 2019; 393(10172): 689-701.;","DOI":"10.1016\/S0140-6736(18)32596-0"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Abdljabbar R, Tammimi DE, Yousef A-M, Mukred SR, Zawiah M. SCN1A polymorphisms influence the anti-epileptic drugs responsiveness in Jordanian epileptic patients. J Med Biochem 2023; 42(2): 214-23.;","DOI":"10.5937\/jomb0-34544"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Gorina YV, Salmina AB, Erofeev AI, Gerasimov EI, Bolshakova AV, Balaban PM, Bezprozvanny IB, Vlasova OL: Astrocyte Activation Markers. Biochemistry (Mosc) 2022; 87(9): 851-70.;","DOI":"10.1134\/S0006297922090012"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Cao DD, Li L, Chan WY: MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases. Int J Mol Sci 2016; 17(6).;","DOI":"10.3390\/ijms17060842"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Gorter JA, Iyer A, White I, Colzi A, van Vliet EA, Sisodiya S, Aronica E: Hippocampal subregion-specific microRNA expression during epileptogenesis in experimental temporal lobe epilepsy. Neurobiol Dis 2014; 62: 508-20.;","DOI":"10.1016\/j.nbd.2013.10.026"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Giorgi FS, Biagioni F , Lenzi P , Frati A, Fornai F: The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations. J Neural Transm (Vienna) 2015; 122(6): 849-62.;","DOI":"10.1007\/s00702-014-1312-1"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Zhao Y , Zhao W , Han Y: Inhibition of mTORC2 improves brain injury in epileptic rats by promoting chaperone-mediated autophagy. Epilepsy Res 2023; 193: 107161.;","DOI":"10.1016\/j.eplepsyres.2023.107161"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Ghafouri-Fard S, Shoorei H, Mohaqiq M, Majidpoor J, Moosavi MA, T aheri M: Exploring the role of non-coding RNAs in autophagy. Autophagy 2022; 18(5): 949-70.;","DOI":"10.1080\/15548627.2021.1883881"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"T ao Z, Feng C, Mao C, Ren J, T ai Y , Guo H, Pu M, Zhou Y , Wang G, Wang M: MiR-4465 directly targets PTEN to inhibit AKT\/mTOR pathway-mediated autophagy. Cell Stress Chaperones 2019; 24(1): 105-13.;","DOI":"10.1007\/s12192-018-0946-6"},{"key":"ref13","unstructured":"Huang WS, Zhu L: MiR-134 expression and changes in inflammatory cytokines of rats with epileptic seizures. Eur Rev Med Pharmacol Sci 2018; 22(11): 3479-84.;"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Chen Z, Brodie MJ, Liew D, Kwan P: Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol 2018; 75(3): 279-86.;","DOI":"10.1001\/jamaneurol.2017.3949"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J, Jr., Forsgren L, French JA, Glynn M et al.: ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55(4): 475-82.;","DOI":"10.1111\/epi.12550"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Raoof R, Bauer S, El Naggar H, Connolly NMC, Brennan GP , Brindley E, Hill T , McArdle H, Spain E, Forster RJ et al. Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy. EBioMedicine 2018; 38: 127-41.;","DOI":"10.1016\/j.ebiom.2018.10.068"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Lu TX, Rothenberg ME: MicroRNA. J Allergy Clin Immunol 2018;141(4): 1202-7.;","DOI":"10.1016\/j.jaci.2017.08.034"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Ma Y: The Challenge of microRNA as a Biomarker of Epilepsy. Curr Neuropharmacol 2018; 16(1): 37-42.;","DOI":"10.2174\/1570159X15666170703102410"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Liu Y , Yu G, Ding YY , Zhang YX: Expression of miR-155 in Serum Exosomes in Children with Epilepsy and Its Diagnostic Value. Dis Markers 2022; 2022: 7979500.;","DOI":"10.1155\/2022\/7979500"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Niu X, Zhu HL, Liu Q, Y an JF , Li ML: MiR-194-5p serves as a potential biomarker and regulates the proliferation and apoptosis of hippocampus neuron in children with temporal lobe epilepsy. J Chin Med Assoc 2021; 84(5): 510-6.;","DOI":"10.1097\/JCMA.0000000000000518"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Yu Y , Du L, Zhang J: Febrile Seizure-Related miR-148a-3p Exerts Neuroprotection by Promoting the Proliferation of Hippocampal Neurons in Children with Temporal Lobe Epilepsy. Dev Neurosci 2021; 43(5): 312-20.;","DOI":"10.1159\/000518352"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Tang X, Wen X, Li Z, Wen D, Lin L, Liu J, Li M: Hsa_circ_0102171 aggravates the progression of cervical cancer through targeting miR-4465\/CREBRF axis. J Cell Physiol 2021; 236(7): 4973-84.;","DOI":"10.1002\/jcp.30210"},{"key":"ref23","unstructured":"Liu J, Zeng Y, Zheng L: Up-regulation of oxidised low-density lipoprotein receptor 1 correlates with decreased miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465, higher recurrence rate, and poor prognosis in ovarian cancer. Histol Histopathol 2023; 38(4): 475-85.;"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Fassio A, Falace A, Esposito A, Aprile D, Guerrini R, Benfenati F: Emerging Role of the Autophagy\/Lysosomal Degradative Pathway in Neurodevelopmental Disorders With Epilepsy. Front Cell Neurosci 2020; 14: 39.;","DOI":"10.3389\/fncel.2020.00039"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Chen C, Zhu T , Gong L, Hu Z, Wei H, Fan J, Lin D, Wang X, Xu J, Dong X et al.: Trpm2 deficiency in microglia attenuates neuroinflammation during epileptogenesis by upregulating autophagy via the AMPK\/mTOR pathway. Neurobiol Dis 2023; 186: 106273.;","DOI":"10.1016\/j.nbd.2023.106273"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Verkhratsky A, Nedergaard M: Physiology of Astroglia. Physiol Rev 2018; 98(1): 239-389.;","DOI":"10.1152\/physrev.00042.2016"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Vezzani A, Ravizza T , Bedner P , Aronica E, Steinhauser C, Boison D: Astrocytes in the initiation and progression of epilepsy. Nat Rev Neurol 2022; 18(12): 707-22.;","DOI":"10.1038\/s41582-022-00727-5"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Alvarez-Garcia V, Tawil Y, Wise HM, Leslie NR: Mechanisms of PTEN loss in cancer: It's all about diversity. Semin Cancer Biol 2019; 59: 66-79.;","DOI":"10.1016\/j.semcancer.2019.02.001"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Dhamija R, Hoxworth JM: Imaging of PTEN-related abnormalities in the central nervous system. Clin Imaging 2020; 60(2): 180-5.;","DOI":"10.1016\/j.clinimag.2019.12.006"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Roquid KAR, Alcantara KMM, Garcia RL: Identification and validation of mRNA 3'untranslated regions of DNMT3B and TET3 as novel competing endogenous RNAs of the tumor suppressor PTEN. Int J Oncol 2020; 56(2): 544-58.;","DOI":"10.3892\/ijo.2019.4947"}],"container-title":["Journal of Medical Biochemistry"],"original-title":["Mehanizam delovanja miR-4465 na PTEN-posredovanu autofagiju astrocita kod epilepsije"],"language":"en","link":[{"URL":"https:\/\/scindeks-clanci.ceon.rs\/data\/pdf\/1452-8258\/2025\/1452-82582506347Z.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T11:14:40Z","timestamp":1757070880000},"score":1,"resource":{"primary":{"URL":"https:\/\/scindeks.ceon.rs\/Article.aspx?artid=1452-82582506347Z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.5937\/jomb0-52626","relation":{},"ISSN":["1452-8258","1452-8266"],"issn-type":[{"type":"print","value":"1452-8258"},{"type":"electronic","value":"1452-8266"}],"subject":[],"published":{"date-parts":[[2025]]}}}