REFERENCES
2. Shang R, Lee S, Senavirathne G, Lai EC. microRNAs in action: biogenesis, function and regulation. Nat Rev Genet. 2023;24:816-33.
3. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843-54.
4. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004;15:185-97.
5. Liao J, Ma L, Guo Y, et al. Deep sequencing of human nuclear and cytoplasmic small RNAs reveals an unexpectedly complex subcellular distribution of miRNAs and tRNA 3′ trailers. PLoS ONE. 2010;5:e10563.
6. Billi M, De Marinis E, Gentile M, Nervi C, Grignani F. Nuclear miRNAs: gene regulation activities. Int J Mol Sci. 2024;25:6066.
7. Liu H, Lei C, He Q, Pan Z, Xiao D, Tao Y. Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer. Mol Cancer. 2018;17:64.
8. Santovito D, Weber C. Non-canonical features of microRNAs: paradigms emerging from cardiovascular disease. Nat Rev Cardiol. 2022;19:620-38.
9. Costa S, La Rocca G, Cavalieri V. Epigenetic regulation of chromatin functions by MicroRNAs and long noncoding RNAs and implications in human diseases. Biomedicines. 2025;13:725.
11. Sessa F, Salerno M, Esposito M, Cocimano G, Pomara C. miRNA dysregulation in cardiovascular diseases: current opinion and future perspectives. Int J Mol Sci. 2023;24:5192.
12. Zhou S, Jin J, Wang J, et al. miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin. 2018;39:1073-84.
13. Nappi F. Non-coding RNA-targeted therapy: a state-of-the-art review. Int J Mol Sci. 2024;25:3630.
14. Kim H, Lee Y, Kim VN. The biogenesis and regulation of animal microRNAs. Nat Rev Mol Cell Biol. 2024;26:276-96.
15. Komatsu S, Kitai H, Suzuki HI. Network regulation of microRNA biogenesis and target interaction. Cells. 2023;12:306.
16. Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2004;24:138-48.
17. Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415-9.
18. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21:4663-70.
19. Chendrimada TP, Gregory RI, Kumaraswamy E, et al. TRBP recruits the dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740-4.
20. Suzuki HI, Katsura A, Yasuda T, et al. Small-RNA asymmetry is directly driven by mammalian Argonautes. Nat Struct Mol Biol. 2015;22:512-21.
21. Iwasaki S, Kobayashi M, Yoda M, et al. Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes. Mol Cell. 2010;39:292-9.
22. Abel Y, Charron C, Virciglio C, et al. The interaction between RPAP3 and TRBP reveals a possible involvement of the HSP90/R2TP chaperone complex in the regulation of miRNA activity. Nucleic Acids Res. 2022;50:2172-89.
23. Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of MicroRNA precursors. Science. 2004;303:95-8.
24. Ritland Politz JC, Zhang F, Pederson T. MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc Natl Acad Sci USA. 2006;103:18957-62.
25. Ritland Politz JC, Hogan EM, Pederson T. MicroRNAs with a nucleolar location. RNA. 2009;15:1705-15.
26. Robb GB, Brown KM, Khurana J, Rana TM. Specific and potent RNAi in the nucleus of human cells. Nat Struct Mol Biol. 2005;12:133-7.
27. Hwang H, Wentzel EA, Mendell JT. A hexanucleotide element directs MicroRNA nuclear import. Science. 2007;315:97-100.
28. Jeffries CD, Fried HM, Perkins DO. Nuclear and cytoplasmic localization of neural stem cell microRNAs. RNA. 2011;17:675-86.
29. Guang S, Bochner AF, Pavelec DM, et al. An argonaute transports siRNAs from the cytoplasm to the nucleus. Science. 2008;321:537-41.
30. Wei Y, Li L, Wang D, Zhang C, Zen K. Importin 8 regulates the transport of mature MicroRNAs into the cell nucleus. J Biol Chem. 2014;289:10270-5.
31. Weinmann L, Höck J, Ivacevic T, et al. Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell. 2009;136:496-507.
32. Schraivogel D, Schindler SG, Danner J, et al. Importin-β facilitates nuclear import of human GW proteins and balances cytoplasmic gene silencing protein levels. Nucleic Acids Res. 2015;43:7447-61.
33. Nishi K, Nishi A, Nagasawa T, Ui-tei K. Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus. RNA. 2013;19:17-35.
34. Sobti M, Mead BJ, Stewart AG, Igreja C, Christie M. Molecular basis for GIGYF-TNRC6 complex assembly. RNA. 2023;29:724-34.
35. Johnson KC, Kilikevicius A, Hofman C, et al. Nuclear localization of Argonaute 2 is affected by cell density and may relieve repression by microRNAs. Nucleic Acids Res. 2024;52:1930-52.
36. Pitchiaya S, Heinicke LA, Park JI, Cameron EL, Walter NG. Resolving subcellular miRNA trafficking and turnover at single-molecule resolution. Cell Rep. 2017;19:630-42.
37. Liu X, Guo J, Lin X, et al. Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms. Eur Heart J. 2021;42:4847-61.
38. Xie R, Yuan S, Hu G, et al. Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts. Mol Ther. 2024;32:1578-94.
39. Zhang Y, Fan M, Zhang X, et al. Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs. RNA. 2014;20:1878-89.
40. Bai Y, Pan B, Zhan X, Silver H, Li J. MicroRNA 195-5p targets Foxo3 promoter region to regulate its expression in granulosa cells. Int J Mol Sci. 2021;22:6721.
41. Wan D, Liang X, Liang F, Zhu M, Zhang C, Zhang S. The role of miR-3188-mediated transcriptional activation of IL-7Rα in tumor immunotherapy research. Mol Immunol. 2026;189:142-52.
42. Zisoulis DG, Kai ZS, Chang RK, Pasquinelli AE. Autoregulation of microRNA biogenesis by let-7 and Argonaute. Nature. 2012;486:541-4.
43. Tang R, Li L, Zhu D, et al. Mouse miRNA-709 directly regulates miRNA-15a/16-1 biogenesis at the posttranscriptional level in the nucleus: evidence for a microRNA hierarchy system. Cell Res. 2011;22:504-15.
44. Wang D, Sun X, Wei Y, et al. Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level. Nucleic Acids Res. 2018;46:2012-29.
45. La Rocca G, Cavalieri V. Roles of the core components of the mammalian miRISC in chromatin biology. Genes. 2022;13:414.
46. El Fatimy R, Zhang Y, Deforzh E, et al. A nuclear function for an oncogenic microRNA as a modulator of snRNA and splicing. Mol Cancer. 2022;21:17.
47. Santovito D, Egea V, Bidzhekov K, et al. Noncanonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis. Sci Transl Med. 2020;12:eaaz2294.
48. Xie H, Qin Z, Ling Z, et al. Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis. Int J Oral Sci. 2023;15:26.
49. Meng F, Han L, Liang Q, Lu S, Huang Y, Liu J. The Lnc-RNA APPAT suppresses human aortic smooth muscle cell proliferation and migration by interacting with MiR-647 and FGF5 in Atherosclerosis. J Endovasc Ther. 2022;30:937-50.
50. Mathiyalagan P, Okabe J, Chang L, Su Y, Du X, El-Osta A. The primary microRNA-208b interacts with polycomb-group protein, Ezh2, to regulate gene expression in the heart. Nucleic Acids Res. 2013;42:790-803.
51. Fan J, Zhang X, Nie X, et al. Nuclear miR-665 aggravates heart failure via suppressing phosphatase and tensin homolog transcription. Sci China Life Sci. 2019;63:724-36.
52. Li H, Fan J, Zhao Y, et al. Nuclear miR-320 mediates diabetes-induced cardiac dysfunction by activating transcription of fatty acid metabolic genes to cause lipotoxicity in the heart. Circ Res. 2019;125:1106-20.
53. Zhan J, Jin K, Ding N, et al. Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction. Mol Ther Nucleic Acids. 2023;31:122-38.
54. Khan AW, Ziemann M, Corcoran SJ, et al. NET silencing by let-7i in postural tachycardia syndrome. JCI Insight. 2017;2:e90183.
55. Di Mauro V, Crasto S, Colombo FS, Di Pasquale E, Catalucci D. Wnt signalling mediates miR-133a nuclear re-localization for the transcriptional control of Dnmt3b in cardiac cells. Sci Rep. 2019;9:9320.
58. Souilhol C, Serbanovic-Canic J, Fragiadaki M, et al. Endothelial responses to shear stress in atherosclerosis: a novel role for developmental genes. Nat Rev Cardiol. 2019;17:52-63.
59. Wei Y, Nazari-Jahantigh M, Neth P, Weber C, Schober A. MicroRNA-126, -145, and -155: a therapeutic triad in atherosclerosis? Arterioscler Thromb Vasc Biol. 2013;33:449-54.
60. Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15:272-84.
61. Theofilis P, Oikonomou E, Vogiatzi G, et al. The role of MicroRNA-126 in atherosclerotic cardiovasculardiseases. Curr Med Chem. 2023;30:1902-21.
62. Schober A, Nazari-Jahantigh M, Wei Y, et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med. 2014;20:368-76.
63. Liu X, Wu J, Tian R, Su S, Deng S, Meng X. Targeting foam cell formation and macrophage polarization in atherosclerosis: the therapeutic potential of rhubarb. Biomed Pharmacother. 2020;129:110433.
64. Ma C, Li Y, Tian M, et al. Gsα regulates macrophage foam cell formation during atherosclerosis. Circ Res. 2024;134:e34-e51.
65. Tian K, Xu Y, Sahebkar A, Xu S. CD36 in Atherosclerosis: pathophysiological mechanisms and therapeutic implications. Curr Atheroscler Rep. 2020;22:59.
66. Crabtree GR, Olson EN. NFAT signaling: choreographing the social lives of cells. Cell. 2002;109:S67-79.
67. Mozafari M, Md Hashim SN, Ahmad Amin Noordin KB, Zainal SA, Azlina A. Nuclear factor of activated T cells (NFAT) proteins as targeted molecules in diseases: a narrative review. Cureus. 2024;16:e75844.
68. Park Y, Yoo S, Kim M, Kim W. The role of calcium-calcineurin-NFAT signaling pathway in health and Autoimmune diseases. Front Immunol. 2020;11:195.
69. Haraszthy V, Zambon J, Trevisan M, Zeid M, Genco R. Identification of periodontal pathogens in Atheromatous plaques. J Periodontol. 2000;71:1554-60.
70. Xie M, Tang Q, Nie J, et al. BMAL1-downregulation aggravates Porphyromonas gingivalis-induced atherosclerosis by encouraging oxidative stress. Circ Res. 2020:126.
71. Park S, Kim I, Han SJ, et al. Oral Porphyromonas gingivalis infection affects intestinal microbiota and promotes atherosclerosis. J Clin Periodontol. 2023;50:1553-67.
72. Rao A, D’souza C, Subramanyam K, et al. Molecular analysis shows the presence of periodontal bacterial DNA in atherosclerotic plaques from patients with coronary artery disease. Indian Heart J. 2021;73:218-20.
73. Šubarić A, Arsić Z, Mihailović Đ, et al. Detecting oral bacteria in abdominal aorta atherosclerotic plaques—how far can they go? Medicina. 2025;61:1976.
74. Meng F, Yan J, Ma Q, et al. Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis. PeerJ. 2018;6:e4246.
75. Lu S, Liang Q, Huang Y, Meng F, Liu J. Definition and review on a category of long non-coding RNA: atherosclerosis-associated circulating lncRNA (ASCLncRNA). PeerJ. 2020;8:e10001.
76. Hang CT, Yang J, Han P, et al. Chromatin regulation by Brg1 underlies heart muscle development and disease. Nature. 2010;466:62-7.
77. Guo S, Hu Y, Ling L, et al. Molecular mechanisms and intervention approaches of heart failure (Review). Int J Mol Med. 2025;56:1-15.
78. Yue P, Xia S, Wu G, et al. Attenuation of cardiomyocyte hypertrophy via depletion Myh7 using CASAAV. Cardiovasc Toxicol. 2020;21:255-64.
79. K N H, Okabe J, Mathiyalagan P, et al. Sex-based Mhrt methylation chromatinizes MeCP2 in the heart. iScience. 2019;17:288-301.
80. Yim E, Peng G, Dai H, et al. Rak functions as a tumor suppressor by regulating PTEN protein stability and function. Cancer Cell. 2009;15:304-14.
81. Jha M, Bhatt LK. Exploring phosphatase and tensin homologue deleted on chromosome ten (PTEN) as a potential therapeutic target for cardiac hypertrophy. ACS Pharmacol Transl Sci. 2025;8:2312-36.
82. Oudit G, Sun H, Kerfant BG, Crackower MA, Penninger JM, Backx PH. The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease. J Mol Cell Cardiol. 2004;37:449-71.
83. Oudit GY, Penninger JM. Cardiac regulation by phosphoinositide 3-kinases and PTEN. Cardiovasc Res. 2008;82:250-60.
84. Nie X, Fan J, Li H, et al. miR-217 promotes cardiac hypertrophy and dysfunction by targeting PTEN. Mol Ther Nucl Acids. 2018;12:254-66.
85. Huo J, Feng Q, Pan S, Fu W, Liu Z, Liu Z. Diabetic cardiomyopathy: early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions. Cell Death Discov. 2023;9:256.
86. Yang J, Sambandam N, Han X, et al. CD36 deficiency rescues lipotoxic cardiomyopathy. Circ Res. 2007;100:1208-17.
87. Rada P, González-Rodríguez Á, García-Monzón C, Valverde ÁM. Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver? Cell Death Dis. 2020;11:802.
88. Goldstein DS, Holmes C, Frank SM, et al. Cardiac sympathetic dysautonomia in chronic orthostatic intolerance syndromes. Circulation. 2002;106:2358-65.
89. Mar PL, Raj SR. Postural orthostatic tachycardia syndrome: mechanisms and new therapies. Annu Rev Med. 2020;71:235-48.
90. Shannon JR, Flattem NL, Jordan J, et al. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med. 2000;342:541-9.
91. Lambert E, Eikelis N, Esler M, et al. Altered sympathetic nervous reactivity and norepinephrine transporter expression in patients with postural tachycardia syndrome. Circ Arrhythm Electrophysiol. 2008;1:103-9.
92. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247-57.
93. Ueda Y, Okano M, Williams C, Chen T, Georgopoulos K, Li E. Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome. Development. 2006;133:1183-92.
94. Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol. 2017;35:238-48.
95. Brillante S, Volpe M, Indrieri A. Advances in MicroRNA therapeutics: from preclinical to clinical studies. Hum Gene Ther. 2024;35:628-48.
96. Kara G, Calin GA, Ozpolat B. RNAi-based therapeutics and tumor targeted delivery in cancer. Adv Drug Delivery Rev. 2022;182:114113.
97. Nappi F, Avtaar Singh SS, Jitendra V, Alzamil A, Schoell T. The roles of microRNAs in the cardiovascular system. Int J Mol Sci. 2023;24:14277.
98. Chakraborty C, Sharma AR, Sharma G, Lee S. Therapeutic advances of miRNAs: a preclinical and clinical update. J Adv Res. 2021;28:127-38.
99. Bauersachs J, Solomon SD, Anker SD, et al. Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: rationale and design of the HF-REVERT trial. Eur J Heart Fail. 2024;26:674-82.
100. Chioccioli M, Roy S, Newell R, et al. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. eBioMedicine. 2022;85:104304.
101. Hinkel R, Penzkofer D, Zühlke S, et al. Inhibition of MicroRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation. 2013;128:1066-75.
102. Bonauer A, Carmona G, Iwasaki M, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324:1710-3.
103. Abplanalp WT, Fischer A, John D, et al. Efficiency and target derepression of anti-miR-92a: results of a first in human study. Nucleic Acid Ther. 2020;30:335-45.
104. Gallo A, Agnese V, Sciacca S, et al. MicroRNA-30d and -483-3p for Bi-ventricular remodelling and miR-126-3p for pulmonary hypertension in advanced heart failure. ESC Heart Fail. 2024;11:155-66.
105. Zernecke A, Bidzhekov K, Noels H, et al. Delivery of MicroRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2:ra81.
106. Gabisonia K, Prosdocimo G, Aquaro GD, et al. MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs. Nature. 2019;569:418-22.
107. Locher MR, Razumova MV, Stelzer JE, Norman HS, Patel JR, Moss RL. Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics. Am J Physiol Heart Circ Physiol. 2009;297:H247-56.
108. Hsieh J, Becklin KL, Givens S, et al. Myosin heavy chain converter domain mutations drive early-stage changes in extracellular matrix dynamics in hypertrophic cardiomyopathy. Front Cell Dev Biol. 2022;10:894635.
109. Mosqueira D, Mannhardt I, Bhagwan JR, et al. CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy. Eur Heart J. 2018;39:3879-92.
110. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513-8.
111. Weber JA, Baxter DH, Zhang S, et al. The MicroRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733-41.
112. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108:5003-8.
113. Mayr M, Zampetaki A, Willeit P, Willeit J, Kiechl S. MicroRNAs within the continuum of postgenomics biomarker discovery. Arterioscler Thromb Vasc Biol. 2013;33:206-14.
114. Vanhaverbeke M, Attard R, Bartekova M, et al. Peripheral blood RNA biomarkers for cardiovascular disease from bench to bedside: a position paper from the EU-CardioRNA COST action CA17129. Cardiovasc Res. 2022;118:3183-97.
115. De Gonzalo-Calvo D, Vea A, Bär C, et al. Circulating non-coding RNAs in biomarker-guided cardiovascular therapy: a novel tool for personalized medicine? Eur Heart J. 2019;40:1643-50.
116. Viereck J, Thum T. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circ Res. 2017;120:381-99.
117. De Boer HC, Van Solingen C, Prins J, et al. Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur Heart J. 2013;34:3451-7.
118. Willeit P, Zampetaki A, Dudek K, et al. Circulating MicroRNAs as novel biomarkers for platelet activation. Circ Res. 2013;112:595-600.
119. Marfella R, Di Filippo C, Potenza N, et al. Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders. Eur J Heart Fail. 2013;15:1277-88.
120. De Gonzalo-Calvo D, Van Der Meer RW, Rijzewijk LJ, et al. Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes. Sci Rep. 2017;7:47.
121. Cheng M, Yang J, Zhao X, et al. Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells. Nat Commun. 2019;10:959.
