Abstract
The RNA Precious Medical Initiative requires a safe, affordable, and sustainable device as an administration tool. Why do microRNA (miRNA) quantum language and artificial intelligence (MIRAI) heal us? Even if deep learning is done by a cool computer machine, the therapeutic tools are present like food, since plants are probably the origin of RNA species. While plant and meat miRNAs in exosomes may be transported daily from food to humans at dinner, edible RNA agents may be of interest in drug discovery upon MIRAI’s deep learning for therapeutic applications. Several plant expression systems are already in place, including edible vaccines, bananas, rice, alfalfa, mushrooms, potatoes, tomatoes, peanuts, and maize. Traditional Chinese herbal medicine has involved diet, acupuncture with burning Moxa to warm the skin, massages with botanical oils, and meditation under cooking incense, all of which are linked to miRNAs. The honeysuckle herb contains MIR2911, which is incorporated into the human circulation system via the intestine, and MIR2911 prevented H5N1 flue infection in mouse lungs and coronavirus disease 2019 (COVID-19) in severe respiratory syndrome human coronavirus 2 (SARS-CoV-2)-infected patients. MIR2097-5p in rice has been reported to be responsible for the low degree of COVID-19 epidemics in Asian countries, including Japan. Therefore, edible miRNA panel agents would solve the inconvenience of chemotherapy through complex information technology using quantum RNA language. Moreover, since maternal undernutrition inheritably influences heart failure in adult offspring via altered miRNAs in the mother’s uterus, these clinical reports suggest that environmental factors may be mediated by transferred miRNA comb genes, which can be passed from mother to child. Thus, Darwinism and Mendelian inheritance are controlled by miRNA gene information from food. MiRNA programmed evolutionary therapeutics may be developed by deep learning or AI. This chapter presents a program analysis diagram (PAD) for using miRNAs to cook therapeutics.
All things are poison and nothing is without poison.
von Hohenheim, T. (Paracelsus)
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alfaradhi MZ, Kusinski LC, Fernandez-Twinn DS, Pantaleão LC, Carr SK et al (2016) Maternal obesity in pregnancy developmentally programs adipose tissue inflammation in young, lean male mice offspring. Endocrinology 157:4246–4256. https://doi.org/10.1210/en.2016-1314
Alsaweed M, Hartmann PE, Geddes DT, Kakulas F (2015) MicroRNAs in breastmilk and the lactating breast: potential immunoprotectors and developmental regulators for the infant and the mother. Int J Environ Res Public Health 12:13981–14020. https://doi.org/10.3390/ijerph121113981
Amendola M, Passerini L, Pucci F, Gentner B, Bacchetta R et al (2009) Regulated and multiple miRNA and siRNA delivery into primary cells by a lentiviral platform. Mol Ther 17:1039–1052. https://doi.org/10.1038/mt.2009.48
Amendola M, Giustacchini A, Gentner B, Naldini L (2013) A double-switch vector system positively regulated transgene expression by endogenous microRNA expression (miR-ON vector). Mol Ther 21:934–946. https://doi.org/10.1038/mt.2013.12
Beg MS, Brenner AJ, Sachdev J, Borad M, Kang YK et al (2016) Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Investig New Drugs 35:180–188. https://doi.org/10.1007/s10637-016-0407-v
Botla SK, Savant S, Jandaghi P, Bauer AS, Mücke O et al (2016) Early epigenetic downregulation of microRNA-192 expression promotes pancreatic cancer progression. Cancer Res 76:4149–4159. https://doi.org/10.1158/0008-5472.CAN-15-0390
Braun CJ, Zhang X, Savelyeva I, Wolff S, Moll UM et al (2008) p53-responsive microRNA 192 and 215 are capable of inducing cell cycle arrest. Cancer Res 68:10094–10104. https://doi.org/10.1158/0008-5472.CAN-08-1569
Chiang K, Shu J, Zempleni J, Cui J (2015) Dietary microRNA database (DMD): an archive database and analytic tool for food-borne microRNAs. PLoS One 10:e0128089. https://doi.org/10.1371/journal.pone.0128089
Colin A, Faideau M, Dufour N, Auregan G, Hassig R et al (2009) Engineered lentiviral vector targeting astrocytes in vivo. Glia 57:667–679. https://doi.org/10.1002/glia.20795
Costello A, Lao N, Clynes M, Barron N (2017) Conditional knockdown of endogenous microRNAs in CHO cells using TET-ON-SanDI sponge vectors. Mehods Mol Biol 1603:87–100. https://doi.org/10.1007/978-1-4939-6972-2_6
del Real G, Jiménez-Baranda S, Mira E, Lacalle RA, Lucas P et al (2004) Statins inhibit HIV-1 infection by downregulating rho activity. J Exp Med 200:541–547. https://doi.org/10.1084/jem.20040061
di Stefano B, Martina S, Gentner B, Ungaro F, Schira G et al (2011) A microRNA-based system for selecting and maintain the pluripotent state in human induced pluripotent stem cells. Stem Cells 29:1684–1695. https://doi.org/10.1002/stem.726
Du C, Fujii YR, Ito M, Harada M, Morikawa E et al (2004) Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of long-evans cinnamon rats, a model of Wilson disease. J Nutr Biochem 15:273–280
Fernandez-Twinn DS, Alfaradhi MZ, Martin-Gronert MS, Duque-Guimaraes DE, Piekarz A et al (2014) Downregulation of IRS-1 in adipose tissue of offspring of obese mice is programmed cell-autonomously through posttranscriptional mechanisms. Mol Metab 3:325–333. https://doi.org/10.1016/j.molmet.2014.01.007
Fujii YR (2013) RNA wave for HIV therapy: foods, stem cells and the RNA information gene. World J AIDS 3:131–146. https://doi.org/10.4236/wja.2013.32018
Fujii YR (2014) RNA information gene diseases: nano-RNA-based medical devices with corporate chemotherapy and gene therapy. In: Nanotechnology RNA (ed) . Wang B CRC Press Taylor & Francis Group, Boca Raton, pp 385–434
Fujii YR (2020) The quantum microRNA immunity in human virus-associated diseases: virtual reality of HBV, HCV and HIV-1 infection, and hepatocellular carcinogenesis with AI machine learning. Arch Clin Biomed Res 4:089–129. https://doi.org/10.26502/acbr.50170092
Fujii YR (2021) Quantum microRNA assessment of COVID-19 RNA vaccine: hidden potency of BNT162b2 SARS-CoV-2 spike RNA as microRNA vaccine. Adv Case Stud 3:000552. https://doi.org/10.31031/AICS.2020.03.000552
Fujii YR (2022) In: Rezaei N (ed) Quantum microRNA surveillance against cancer: parallel dimensional analysis of integrated networks by quantum microRNA language in female genital neoplasms. Interdisciplinary Cancer Research Springer Nature, New York, pp 1–24. https://doi.org/10.1007/16833_2022_4
Fujii YR (2023) The microRNA quantum code book. Springer Nature, Singapore
Geisler A, Jungmann A, Kurreck J, Poller W, Katus HA et al (2011) microRNA122-regulated transgene expression increases specificity of cardiac gene transfer upon intravenous delivery of AAV9 vectors. Gene Ther 18:199–209. https://doi.org/10.1038/ft.2010.141
Geisler A, Schön C, Größl T, Pinkert S, Stein EA et al (2013) Application of mutated miR-206 target sites enables skeletal muscle-specific silencing of transgene expression of cardiotropic AAV9 vectors. Mol Ther 21:924–933. https://doi.org/10.1038/mt.2012.276
Gekonge B, Raymond AD, Yin X, Kostman J, Mounzer K et al (2012) Retinoblastoma protein induction by HIV viremia or CCR5 in monocytes exposed to HIV-1 mediates protection from activation-induced apoptosis: ex vivo and in vitro study. J Leukoc Biol 92:397–405. https://doi.org/10.1189/jlb.1111552
Georges SA, Biery MC, Kim S, Schelter JM, Guo J et al (2008) Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR-192 and miR-215. Cancer Res 68:10105–10112. https://doi.org/10.1158/0008-5472.CAN-08-1846
Gray C, Li M, Reynolds CM, Vickers MH (2014) Let-7 miRNA profiles are associated with the reversal of left ventricular hypertrophy and hypertension in adult male offspring from mothers undernourished during pregnancy following preweaning growth hormone treatment. Endocrinology 155:4808–4817. https://doi.org/10.1210/en.2014-1567
Jeong D, Kim J, Nam J, Sun H, Lee YH et al (2015) MicroRNA-124 links p53 to the NF-kB pathway in B-cell lymphoma. Leukemia 29:1868–1874. https://doi.org/10.1038/leu.2015.101
Kim YS, Park SJ, Lee YS, Kong HK, Park JH (2016) miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer. Oncotarget 7:42261–42273. https://doi.org/10.18632/oncotarget.9950
Krattinger R, Boström A, Schiöth HB, Thasler WE, Mwinyi J et al (2016) microRNA-192 suppresses the expression of the farnesoid X receptor. Am J Physiol Gastrointest Liver Physiol 310:G1044–G1051. https://doi.org/10.1152/ajpgi.00297.2015
Li S, Li F, Niu R, Zhang H, Cui A et al (2015) Mir-192 suppresses apoptosis and promote proliferation in esophageal squamous cell carcinoma by targeting Bim. Int J Clin Exp Pathol 8:8048–8056
Lian J, **g Y, Dong Q, Huan L, Chen D et al (2015) miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma. Oncotarget 7:2672–2683. https://doi.org/10.18632/oncotarget.6603
Liu L, Yi H, Wang C, He H, Li P et al (2016) Integrated nanovaccine with microRNA-148a inhibition reprograms tumor-associated dendritic cells by modulating miR-148a/DNMT1/SOCS1 axis. J Immunol 197:1231–1241. https://doi.org/10.4049/jimmunol.1600182
Milliken S (1998) HIV and cancer. In: Saksena N (ed) Human immunodeficiency viruses biology, immunology and molecular biology. Medical Syatems S.p.A., Genoa, pp 475–499
Moore R, Ooi HK, Kang T, Bleris L, Ma L (2015) MiR-192-mediated positive feedback loop controls the robustness of stress-induced p53 oscillations in breast cancer cells. PLoS Comput Biol 11:e1004653. https://doi.org/10.1371/journal.pcbi.1004653
Qiao C, Yuan Z, Li J, He B, Zheng H et al (2011) Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver. Gene Ther 18:403–410. https://doi.org/10.1038/gt.2010.157
Rawlings SA, Ill FA, Kozhaya L, Torres VJ, Unutmaz D (2015) Elimination of HIV-1-infected primary T-cell reservoirs in an in vitro model of latency. PLoS One 10:e0126917. https://doi.org/10.1371/journal.pone.0126917
Romani B, Baygloo NS, Aghasadeghi MR, Allahbakhshi E (2015) HIV-1 Vpr enhances proteasomal degradation of MCM10 DNA replication factor through the Cil4-DDB1[VprBP] E3 ubiquitin ligase to induce G2/M cell cycle. J Biol Chem 290:17380–17389. https://doi.org/10.1074/jbc.M115.641522
Sachdeva R, Jönsson ME, Nelander J, Krikeby A, Guibentif C et al (2010) Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors. Pro Natl Acad Sci USA 107:11602–11607. https://doi.org/10.1073/pnas.1006568107
Shimura M, Toyoda Y, Iijima K, Kinomoto M, Tokunaga K et al (2011) Epigenetic displacement of HP1 from heterochromatin by HIV-1 Vpr causes premature sister chromatid separation. J Cell Biol 194:721–735. https://doi.org/10.1083/jcb.201010118
Shu J, Chiang K, Zempleni J, Cui J (2015) Computational characterization of exogenous microRNAs that can be transferred into human circulation. PLoS One 10:e0140587. https://doi.org/10.1371/journal.pone.0140587
Simmons GE Jr, Taylor HE, Hildreth JE (2012) Caveolin-1 suppresses human immunodeficiency virus-1 replication by inhibiting acetylation of NF-kB. Virology 432:110–119. https://doi.org/10.1016/j.virol.2012.05.016
Wang H, Liu B, Liu X, Li Z, Yu XF et al (2014) Identification of HIV-1 vif regions required for CBF-β interaction and APOBEC3 suppression. PLoS One 9:e95738. https://doi.org/10.1371/journal.pone.000095738
Williams DW, Calderon TM, Lopez L, Carvallo-Torres L, Gaskill PJ et al (2013) Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One 8:e69270. https://doi.org/10.1371/journal.pone.0069270
**e J, **e Q, Zhang H, Ameres SL, Hung JH et al (2011) MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression. Mol Ther 19:526–535. https://doi.org/10.1038/mt.2010.279
You X, Zhang Z, Fan J, Cui Z, Zhang XE (2012) Functionally orthologous viral and cellular microRNAs studied by a novel dual-fluorescent reporter system. PLoS One 7:e36157. https://doi.org/10.1371/journal.pone.0036157
Zheng J, Zhang Q, Mul JD, Yu J, Qi C et al (2016) Maternal high-calorie diet is associated with altered hepatic microRNA expression and impaired metabolic health in offspring at weaning age. Endocrine 54:70–80. https://doi.org/10.1007/s12020-016-0959-9
Zhou Z, Li X, Liu J, Dong L, Chen Q et al (2015) Honeysuckle-encoded atypical microRNA2911 directly targets influenza a viruses. Cell Res 25:39–49. https://doi.org/10.1038/cr.2014.130
Zhou LK, Zou Z, Jiang XM, Zheng Y, Chen X et al (2020a) Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients. Cell Discov 6:54. https://doi.org/10.1038/s41421-020-00197-3
Zhou Z, Zhou Y, Jiang XM, Wang Y, Chen X et al (2020b) Decreased HD-MIR2911 absorption in human subjects with the SIDT1 polymorphism fails to inhibit SARS-CoV-2 replication. Cell Discov 6:63. https://doi.org/10.1038/s41421-020-00206-5
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Fujii, Y.R. (2023). Deep Learning of miRNAs for Therapeutic Applications. In: The MicroRNA 2000 Transformer. Springer, Singapore. https://doi.org/10.1007/978-981-99-3165-1_11
Download citation
DOI: https://doi.org/10.1007/978-981-99-3165-1_11
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-99-3164-4
Online ISBN: 978-981-99-3165-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)