Şizofreni Tanı ve Tedavisinde MikroRNA’ların Rolü

Yıl 2022, Cilt: 4 Sayı: 3, 278 - 287, 27.09.2022

Elif Kağızman Orçun Avşar

Öz

Şizofreni genellikle belirgin halüsinasyonlar veya delüzyonlar ile ilerleyen, diğer fonksiyonel bozulmalarla değişkenlik gösteren, kronik ve sık relapslarla seyreden klinik bir hastalıktır. MicroRNA'lar (miRNA'lar), gen ekspresyonunun transkripsiyon sonrası düzenlenmesine katılan, 22-25 nükleotid uzunluğunda, küçük, endojen ve kodlayıcı olmayan, evrim süresince iyi korunmuş, tek iplikli RNA molekülleridir. Son yıllarda yapılan çalışmalar, mikroRNA’ların nöropsikiyatrik bozuklukların ortaya çıkmasında etkili olduklarını ve anormal ekspresyonlarının potansiyel biyobelirteçler olarak kullanılabileceğini ve bu hastalıkların tedavisi açısından da önemli olduklarını göstermektedir. Bu çalışmada şizofreni ile mikroRNA’lar arasındaki ilişki ve tanı ve tedavi açısından önemi açıklanmaya çalışılacaktır.

Anahtar Kelimeler

Şizofreni, miRNA, Biyobelirteç

Kaynakça

• Akaneya, Y. (2007). The remarkable mechanism of prostaglandin E2 on synaptic plasticity. Gene Regul. Syst. Biol, 1, 83–89.
• Arroyo, J. D., Chevillet, J. R., Kroh, E. M., Ruf, I. K., Pritchard, C. C., Gibson, D. F., et al. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA, 108:5003–8. doi: 10.1073/pnas.1019055108
• Aydın, H. (2005). Synopsis of Psychiatry, İstanbul, Güneş Kitabevi, 2: 134-153
• Babiarz, J. E., Ruby, J. G., Wang, Y., Bartel, D. P., (2008). Blelloch R. Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev, 22:2773–2785.
• Bak, M., Silahtaroglu, A., Moller, M., et al. (2008). MicroRNA expression in the adult mouse central nervous system. RNA; 14, 432-444
• Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116(2), 281. doi: 10.1016/S0092-8674(04)00045-5.
• Bhat, S., Dao, D. T., Terrillion, C. E., Arad, M., Smith, R. J., Soldatov, N. M., Gould, T. D. (2012). CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease. Prog. Neurobiol. 99, 1–14.
• Breder, C. D., Dewitt, D., Kraig, R. P. (1995). Characterization of inducible cyclooxygenase in rat brain. J. Comp. Neurol. 355, 296–315
• Brzozka, M. M., Radyushkin, K., Wichert, S. P., Ehrenreich, H., Rossner, M. J. (2010). Cognitive and sensorimotor gating impairments in transgenic mice overexpressing the schizophrenia susceptibility gene Tcf4 in the brain. Biol. Psychiatry. 68, 33–40
• Cardo, L. F., Coto, E., Mena, L., Ribacoba, R., Moris, G., Menendez, M., Alvarez, V. (2013). Profile of microRNAs in the plasma of parkinson’s disease patients and healthy controls. J. Neurol. 260, 1420–1422. doi: 10.1007/s00415-013-6900-8.
• Dan-Dan Cao, Lu Li, and Wai-Yee Chan. (2016). MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases. Int. J. Mol. Sci. 17(6), 842.doi: 10.33900/ijms17060842
• Davis, G. M., Haas, M. A., Pocock, R. (2015). MicroRNAs: Not “fine-tuners” but key regulators of neuronal development and function. Front. Neurol. 6, 245. doi: 10.3389/fneur.2015.00245. Denli, A. M., Tops, B. B., Plasterk, R. H., Ketting, R. F., Hannon, G. J. (2004). Nature. 432(7014), 231-5.
• Ebert, M. S., Neilson, J. R. ve Sharp, P. A. (2007). MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat. Methods, 4, 721–726.
• Emul, M., Kalelioğlu, T. (2015). Etiology of cardiovascular disease in patients with schizophrenia: current perspectives. Neuropsychiatr Dis Treat, 11, 2493-2503.
• Ertuğrul, A. (2010). Şizofreninin Nörobiyolojisi, Temel Psikofarmakoloji, Ankara, 1: 354,
• Gentner, B. et al. (2009). Stable knockdown of microRNA in vivo by lentiviral vectors. Nat. Methods 6, 63–66
• Girgenti, M. J., LoTurco, J. J., Maher, B. J. (2012). ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2. PLoS One, 7(2): e32404. https://doi.org/10.1371/journal.pone.0032404.
• Gotz, M., Huttner, W. B. (2005). The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol. 6, 777–788. doi: 10.1038/nrm1739.
• Guella, I., Sequeira, A., Rollins, B., Morgan, L., Torri, F., van Erp, TG., Myers, R. M., Barchas, J. D., Schatzberg, A. F., Watson, S. J., et al. (2013). Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex. J. Psychiatr. Res. 47, 1215–1221.
• Han, J., Lee, Y., Yeom, K. H., Kim, Y. K., Jin, H., Kim, V. N., (2004). The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 18(24), 3016-3027.
• Hansen, K. F., Karelina, K., Sakamoto, K., et al. (2013). MiRNA132: a dynamic regulator of cognitive capacity. Brain Struct Funct. 218, 817-831.
• Haqqani, A. S., Delaney, C. E., Tremblay, T. L., Sodja, C., Sandhu, J. K., Stanimirovic, D. B. (2013). Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells. Fluids Barriers CNS. 10(1), 4. doi: 10.1186/2045-8118-10-4.
• Hossain, S., Akaike, T., Chowdhury, E. H. (2010). Current approaches for drug delivery to central nervous system. Curr Drug Deliv. 7, 389‐397. Ipsaro, J. J., Joshua-Tor, L. (2015). From guide to target: molecular insights into eukaryotic RNA-interference machinery. Nat Struct Mol Biol. 22, 20–8. doi: 10.1038/nsmb.2931
• Junn, E., Mouradian, M. M. (2012). MicroRNAs in Neurodegenerative Diseases and Their Therapeutic Potential. Pharmacol Ther, 133, 142-150.
• Kaleb, M. Pauley, Seunghee, C., and Edward K. L. Chan. (2009). MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 32(3-4), 189–194. doi:10.1016/j.jaut.2009.02.012
• Kaplan ve Sadock. (2005). Klinik Psikiyatri. Synopsis of Psychiatry Ninthedition.’den. Çeviri editörü: Hamdullah Aydın. 34-154, 2. baskı. Güneş kitabevi. İstanbul.
• Kasinski, A. L., Slack, F. J. (2012). Arresting the Culprit: Targeted Antagomir Delivery to Sequester Oncogenic miR-221 in HCC. Mol. Ther. Nucleic Acids. 1(3): e12.
• Kim, A. H., Parker, E. K., Williamson, V., McMichael, G. O. (2012). Fanous, A.H.; Vladimirov, V.I. Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137. Schizophr. Res, 141, 60–64
• Kluiver, J. et al. (2012). Rapid generation of microRNA sponges for microRNA inhibition. PloS One, 7(1): e29275.
• Krek, A., Grun, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., et al. (2005). Combinatorial microRNA target predictions. Nat Genet. 37(5), 495–500. doi: 10.1038/ng1536.
• Kunej, T., Godnic, I., Horvat, S., Zorc, M., Calin, G. A. (2012). Cross talk between microRNA and coding cancer genes. Cancer J. 18, 223–231
• Kwon, E., Wang, W., Tsai, L. H. (2013). Validation of schizophrenia-associated genes CSMD1, C10orf26, CACNA1C and TCF4 as miR-137 targets. Mol Psychiatry. 18, 11–12.
• Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J. et al. (2003). The nuclear RNase III Drosha initiates mikroRNA processing. Nature 425(6956),415-9.
• Lee, Y., Jeon, K., Lee, J. T., Kim, S., Kim, V. N. (2002). MicroRNA maturation: stepwise processing and subcellular localization. European Molecular Biology Organization, 21, 4663-4670
• Lewis, B. P., Burge, C. B., Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120(1), 15–20. doi: 10.1016/j.cell.2004.12.035.
• Liu, L., Yuan, G., Cheng, Z., Zhang, G., Liu, X., Zhang, H. (2013). Identification of the mRNA expression status of the dopamine d2 receptor and dopamine transporter in peripheral blood lymphocytes of schizophrenia patients. PLoS One. 8(9), e75259.
• Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E., Kutay, U. (2004). Nuclear export of microRNA precursors. Science, 303(5654),95-8.
• Malmevik, J., Petri, R., Knauff, P., et al. (2016). Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs inhippocampal neurons. Scientific Reports, 6, 1-14.
• Mellios, N., et al. (2010). Gender-Specific reduction of estrogen-sensitive small RNA, miR-30b, in subjects with schizophrenia. Schizophr. Bull. 38(3),433-43.
• Messias, E. L., Chen, C., Eaton, W. W. (2007). Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin N Am. 30(3), 323–338. doi: 10.1016/j.psc.2007.04.007.
• Miller, B. H., Wahlestedt, C. (2010). MicroRNA dysregulation in psychiatric disease. Brain Res. 1338, 89–99. doi: 10.1016/j.brainres.2010.03.035.
• Miller, J. D., Ganat, Y. M., Kishinevsky, S., Bowman, R. L., Liu, B., Tu, E. Y., Mandal, P. K., Vera, E., Shim, J. W., Kriks, S., et al. (2013). Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell. 13, 691–705. doi: 10.1016/j.stem.2013.11.006.
• Mitchell, P. S., Parkin. R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan E. L, et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105(30),10513-8. doi: 10.1073/pnas.0804549105
• Mondol, V., Pasquinelli, A. E. (2012). Let's make it happen: the role of let-7 microRNA in development. In Current topics in developmental biology: microRNAs in development (ed. Hornstein E), Academic Press, Waltham, MA. 1–30
• Narayan, A., Bommakanti, A., Patel, A. A. (2015). High-throughput RNA profiling via up-front sample parallelization. Nat. Methods. 12, 343–399. doi: 10.1038/nmeth.3311.
• Narry, K. V. (2005). Small RNAs: Classification, Biogenesis, and Function. Mol Cells, 19(1), 1-15
• Nowak, J. S., Michlewski, G. (2013). MiRNAs in development and pathogenesis of the nervous system. Biochem Soc Trans. 41(4), 815–820. doi: 10.1042/BST20130044.
• O'Brien, J., Hayder, H., Zayed, Y., Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 3,9,402.
• Okada, C., Yamashita, E., Lee, SJ., Shibata, S., Katahira, J., Nakagawa, A., Yoneda, Y., Tsukihara, T., (2009). A high-resolution structure of the pre-microRNA nuclear export machinery. Science. 326(5957),1275-9.
• Okamura, K., Hagen, J. W., Duan, H., Tyler, D. M., Lai, E. C., (2007). The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell. 130:89–100
• Perkins, D. O., et al. (2007) microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol, 8(2), R27.
• Pitchiaya, S., Heinicke, L. A., Park, J. I., Cameron, E. L., Walter, N. G., (2017). Resolving subcellular miRNA trafficking and turnover at single-molecule resolution. Cell Rep. 19, 630–42. doi: 10.1016/j.celrep.2017.03.075
• Rajasethupathy, P., Fiumara, F., Sheridan, R., Betel, D., Puthanveettil, S. V., Russo, J. J., et al. (2009). Characterization of small RNAs in aplysia reveals a role for miR-124 in constraining synaptic plasticitythrough CREB. Neuron, 63, 803–817.
• Rie, D., Abugessaisa, I., Alam, T., Arner, E., Arner, P., Ashoor, H., et al. (2017). An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat Biotechnol. 35(9), 872-878. doi: 10.1038/nbt.3947.
• Roberts, T. C., and Wood, M. J. A., (2013). Therapeutic targeting of non-coding RNAs. Essays Biochem; (54), 127–145.
• Sang, N., Zhang, J., Marcheselli, V., Bazan, N. G., Chen, C., (2005). Postsynaptically synthesized prostaglandin E2 (PGE2) modulates hippocampal synaptic transmission via a presynaptic PGE2 EP2 receptor. J. Neurosci. 25(43), 9858–9870. doi: 10.1523/JNEUROSCI.2392-05.2005
• Saydam, F., Değirmenci, İ., Güneş, H. V. (2011). Mikro RNA’lar ve kanser. Medical Journal, 38(1), 113-20.
• Schratt, G., (2011) microRNAs at the synapse. Nat. Rev. Neurosci. 12, 182. doi: 10.1038/nrn3010.
• Silber, J., Lim, D. A., Petritsch, C., Persson, A. I., Maunakea, A. K., Yu, M., Vandenberg, S. R., Ginzinger, D. G., James, C. D., Costello, J. F., et al. (2008). MiR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 6, 14. doi: 10.1186/1741-7015-6-14.
• Smalheiser, N. R., Lugli, G., (2009) microRNA regulation of synaptic plasticity. Neuromolecular Med, 11, 133–140.
• Smrt, R. D., et al. (2010) MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells, 28, 1060-1070
• 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 ımprovement in schizophrenia patients before and after antipsychotic treatment. JPsychiatr Res, 54, 134–140
• Sun, E., Shi, Y. (2015). MicroRNAs: small molecules with big roles in neurodevelopment and diseases. Exp Neurol. 268, 46–53. doi: 10.1016/j.expneurol.2014.08.005.
• Sun, G., Ye, P., Murai, K., Lang, M.F., Li, S., Zhang, H., Li, W., Fu, C., Yin, J., Wang, A., et al. (2011). MiR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells. Nat. Commun. 2, 529.
• Trang, P., Medina, PP., Wiggins, JF., et al. (2009). Regression of murine lung tumors by the let-7 microRNA. Oncogene. 29(11), 1580-7. doi: 10.1038/onc.2009.445.
• Van Spronsen, M., van Battum, E.Y., Kuijpers, M., Vangoor, V.R., Rietman, M.L., Pothof, J., Gumy, L.F., van IJcken, W.F.J., Akhmanova, A., Pasterkamp, R.J., et al. (2013). Developmental and activity-dependent miRNA expression profiling in primary hippocampal neuron cultures. PLoS ONE. 8, e74907. doi: 10.1371/journal.pone.0074907
• Velagapudi, SP., Gallo, SM., Disney, MD., (2014). Sequence-based design of bioactive small molecules that target precursor microRNAs. Nature Chem. Biol.;10(4), 291–297.
• Viswanathan, G.Q., Daley, S.R., (2010) Lin28: a microRNA regulator with a macro role. Cell, 140, 445-449
• Wayman, GA., Davare, M., Ando, H., Fortin, D., Varlamova, O., Cheng, HYM., et al. (2008) An activity-regulated microRNA controls dendritic plasticity by down-regulatingp250GAP. Proc Natl Acad Sci U S A, 105, 9093–9098.
• Yang, JS., Maurin, T., Robine, N., Rasmussen, KD., Jeffrey, KL., Chandwani, R., Papapetrou, EP., Sadelain, M., O'Carroll, D., Lai, EC., (2010). Proc Natl Acad Sci ABD 107 (34): 15, 163-8.
• Yang, Y., Shu, X., Liu, D., et al. (2012). EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation. Neuron; 73, 774-788.
• Zhu, Y., et al. (2009) A MicroRNA gene is hosted in an intron of a schizophrenia-susceptibility gene Schizophr. Res, 1-4.