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Saiyed AN, Vasavada AR, Johar SRK. Recent trends in miRNA therapeutics and the application of plant miRNA for prevention and treatment of human diseases. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2022; 8:24. [PMID: 35382490 PMCID: PMC8972743 DOI: 10.1186/s43094-022-00413-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/21/2022] [Indexed: 02/17/2023] Open
Abstract
Background Researchers now have a new avenue to investigate when it comes to miRNA-based therapeutics. miRNAs have the potential to be valuable biomarkers for disease detection. Variations in miRNA levels may be able to predict changes in normal physiological processes. At the epigenetic level, miRNA has been identified as a promising candidate for distinguishing and treating various diseases and defects. Main body In recent pharmacology, plants miRNA-based drugs have demonstrated a potential role in drug therapeutics. The purpose of this review paper is to discuss miRNA-based therapeutics, the role of miRNA in pharmacoepigenetics modulations, plant miRNA inter-kingdom regulation, and the therapeutic value and application of plant miRNA for cross-kingdom approaches. Target prediction and complementarity with host genes, as well as cross-kingdom gene interactions with plant miRNAs, are also revealed by bioinformatics research. We also show how plant miRNA can be transmitted from one species to another by crossing kingdom boundaries in this review. Despite several unidentified barriers to plant miRNA cross-transfer, plant miRNA-based gene regulation in trans-kingdom gene regulation may soon be valued as a possible approach in plant-based drug therapeutics. Conclusion This review summarised the biochemical synthesis of miRNAs, pharmacoepigenetics, drug therapeutics and miRNA transkingdom transfer.
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Affiliation(s)
- Atiyabanu N. Saiyed
- Department of Cell and Molecular Biology, Iladevi Cataract and IOL Research Centre, Ahmedabad, Gujarat India
- Ph.D. scholar of Manipal Academy of Higher Education, Manipal, Karnataka India
| | - Abhay R. Vasavada
- Department of Cell and Molecular Biology, Iladevi Cataract and IOL Research Centre, Ahmedabad, Gujarat India
| | - S. R. Kaid Johar
- Department of Zoology, BMTC, Human Genetics, USSC, Gujarat University, Ahmedabad, Gujarat India
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Danielson KM, Shah R, Yeri A, Liu X, Camacho Garcia F, Silverman M, Tanriverdi K, Das A, Xiao C, Jerosch-Herold M, Heydari B, Abbasi S, Van Keuren-Jensen K, Freedman JE, Wang YE, Rosenzweig A, Kwong RY, Das S. Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction. EBioMedicine 2018; 32:172-181. [PMID: 29779700 PMCID: PMC6020713 DOI: 10.1016/j.ebiom.2018.05.013] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 05/07/2018] [Accepted: 05/08/2018] [Indexed: 01/08/2023] Open
Abstract
Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with "beneficial" (decrease LVESVI ≥ 20%, n = 11) and "adverse" (increase LVESVI ≥ 15%, n = 11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n = 331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm.
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Affiliation(s)
- Kirsty M Danielson
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery & Anaesthesia, University of Otago, Wellington 6242, New Zealand
| | - Ravi Shah
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Ashish Yeri
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Xiaojun Liu
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Fernando Camacho Garcia
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Michael Silverman
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Kahraman Tanriverdi
- Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
| | - Avash Das
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Chunyang Xiao
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Michael Jerosch-Herold
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Bobak Heydari
- Division of Cardiology, Department of Cardiac Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada
| | - Siddique Abbasi
- Noninvasive Cardiovascular Imaging Section, Cardiovascular Division, Department of Medicine and Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | | | - Jane E Freedman
- Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
| | - Yaoyu E Wang
- Dana Farber Cancer Institute Center for Computational Biology, Harvard Medical School, Boston, MA 02115, USA
| | - Anthony Rosenzweig
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Raymond Y Kwong
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Saumya Das
- Cardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
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Das S, Vasanthi HR, Parjapath R. MitomiRs Keep the Heart Beating. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 982:431-450. [PMID: 28551801 DOI: 10.1007/978-3-319-55330-6_23] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
In this chapter, we focus on the microRNAs (miRNAs or miRs) that have been found in the mitochondrial compartment, and target either mitochondrial or nuclear encoded genes present in mitochondria, leading to an alteration of mitochondrial function. We term this subset of miRNAs as "MitomiRs".
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Affiliation(s)
- Samarjit Das
- Department of Pathology, Cardiovascular Division, Johns Hopkins University, Baltimore, MD, 21205, USA.
| | - Hannah R Vasanthi
- Department of Biotechnology, Pondicherry University, Puducherry, India
| | - Ramesh Parjapath
- Department of Biotechnology, Pondicherry University, Puducherry, India
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Srinivasan H, Das S. Mitochondrial miRNA (MitomiR): a new player in cardiovascular health. Can J Physiol Pharmacol 2015; 93:855-61. [DOI: 10.1139/cjpp-2014-0500] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Cardiovascular disease is one of the major causes of human morbidity and mortality in the world. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and are known to be involved in the pathogenesis of heart diseases, but the translocation phenomenon and the mode of action in mitochondria are largely unknown. Recent mitochondrial proteome analysis unveiled at least 2000 proteins, of which only 13 are made by the mitochondrial genome. There are numerous studies demonstrating the translocation of proteins into the mitochondria and also translocation of ribosomal RNA (viz., 5S rRNA) into mitochondria. Recent studies have suggested that miRNAs contain sequence elements that affect their subcellular localization, particularly nuclear localization. If there are sequence elements that direct miRNAs to the nucleus, it is also possible that similar sequence elements exist to direct miRNAs to the mitochondria. In this review we have summarized most of the miRNAs that have been shown to play an important role in mitochondrial function, either by regulating mitochondrial genes or by regulating nuclear genes that are known to influence mitochondrial function. While the focus of this review is cardiovascular diseases, we also illustrate the role of mitochondrial miRNA (MitomiR) in the initiation and progression of various diseases, including cardiovascular diseases, metabolic diseases, and cancer. Our goal here is to summarize the miRNAs that are localized to the mitochondrial fraction of cells, and how these miRNAs modulate cardiovascular health.
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Affiliation(s)
- Hemalatha Srinivasan
- Department School of Life Sciences, B.S. Abdur Rahman University, Chennai, Tamil Nadu, India
| | - Samarjit Das
- Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
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Boštjančič E, Glavač D. miRNome in myocardial infarction: Future directions and perspective. World J Cardiol 2014; 6:939-958. [PMID: 25276296 PMCID: PMC4176804 DOI: 10.4330/wjc.v6.i9.939] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 03/28/2014] [Accepted: 06/27/2014] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs), which are small and non-coding RNAs, are genome encoded from viruses to humans. They contribute to various developmental, physiological and pathological processes in living organisms. A huge amount of research results revealed that miRNAs regulate these processes also in the heart. miRNAs may have cell-type-specific or tissue-specific expression patterns or may be expressed ubiquitously. Primary studies of miRNA involvement in hypertrophy, heart failure and myocardial infarction analyzed miRNAs that are enriched in or specific for cardiomyocytes; however, growing evidence suggest that other miRNAs, not cardiac or muscle-specific, play a significant role in cardiovascular disease. Abnormal miRNA regulation has been shown to be involved in cardiac diseases, suggesting that miRNAs might affect cardiac structure and function. In this review, we focus on miRNAs that have been found to contribute to the pathogenesis of myocardial infarction (MI) and the response post-MI and characterized as diagnostic, prognostic and therapeutic targets. The majority of these studies were performed using mouse and rat models of MI, with a focus on the identification of basic cellular and molecular pathways involved in MI and in the response post-MI. Much research has also been performed on animal and human plasma samples from MI individuals to identify miRNAs that are possible prognostic and/or diagnostic targets of MI and other MI-related diseases. A large proportion of research is focused on miRNAs as promising therapeutic targets and biomarkers of drug responses and/or stem cell treatment approaches. However, only a few studies have described miRNA expression in human heart tissue following MI.
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Feng Z, Takahashi R, Nakamura T, Sato D, Shirasawa N, Nakayama A, Kurashige S, Kosawada T, Kitajima T, Umezu M. Expression of microRNA-1, microRNA-133a and Hand2 protein in cultured embryonic rat cardiomyocytes. In Vitro Cell Dev Biol Anim 2014; 50:700-6. [PMID: 24789724 DOI: 10.1007/s11626-014-9755-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 04/05/2014] [Indexed: 12/12/2022]
Abstract
In this study, we investigated the expression of the pathway, SRF-microRNA-1/microRNA-133a-Hand2, in the Wistar rat embryonic ventricular cardiomyocytes under conventional monolayer culture. The morphological observation of the cultured cardiomyocytes and the mRNA expression levels of three vital constituent proteins, MLC-2v, N-cadherin, and connexin43, demonstrated the immaturity of these cultured cells, which was featured by less myofibril density, immature sarcomeric structure, and significantly lower mRNA expression of the three constituent proteins than those in neonatal ventricular samples. More importantly, results in this study suggest that the change of SRF-microRNA-1/microRNA-133a-Hand2 pathway results into the attenuation of the Hand2 repression in cultured cardiomyocytes. These outcomes are valuable to understand the cellular state as embryonic cardiomyocytes to be in vitro model and might be useful for the assessment of engineered cardiac tissue and cardiac differentiation of stem cells.
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Affiliation(s)
- Zhonggang Feng
- Graduate School of Science and Engineering, Yamagata University, Yonezawa-shi, Japan,
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