Role of microRNA-30c in lipid metabolism, adipogenesis, cardiac remodeling and cancer

Irani, Sara; Hussain, M. Mahmood

doi:10.1097/mol.0000000000000162

Cited by 42 publications

(33 citation statements)

References 83 publications

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“…Looking at other fundamental molecules, also LDLR expression was shown to be targeted by miR-214 [53], while other miRs (miR-125a and miR-455 [54]) regulate scavenger receptor class B type I (SR-BI) expression. Other molecules involved in lipid metabolism besides those mentioned in previous paragraphs are also regulated by miRs (e.g., MTP, protein important for lipoprotein formation, is regulated by miR-30c [55], or Lectin-like oxidized LDL receptor-1 (LOX-1), one of the scavenger receptors, is targeted by let-7g [56]). Collectively, these data suggest a strong potential of miRs in the posttranscriptional regulation of lipid metabolism-related genes and prompt potential usage of selected miRs as tools to monitor and treat metabolic, cardiovascular and especially cardiometabolic disorders, including atherosclerosis [57].…”

Section: Micrornas Involvement In Lipid Metabolismmentioning

confidence: 99%

Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis

Novák

Olejníčková

Tkáčová

et al. 2015

Advances in Experimental Medicine and Biology

104

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MicroRNAs (miRNAs, miRs) represent a group of powerful and versatile posttranscriptional regulators of gene expression being involved in the fine control of a plethora of physiological and pathological processes. Besides their well-established crucial roles in the regulation of cell cycle, embryogenesis or tumorigenesis, these tiny molecules have also been shown to participate in the regulation of lipid metabolism. In particular, miRs orchestrate cholesterol and fatty acids synthesis, transport, and degradation and low-density and high-density lipoprotein (LDL and HDL) formation. It is thus not surprising that they have also been reported to affect the development and progression of several lipid metabolism-related disorders including liver steatosis and atherosclerosis. Mounting evidence suggests that miRs might represent important “posttranscriptional hubs” of lipid metabolism, which means that one miR usually targets 3′-untranslated regions of various mRNAs that are involved in different steps of one precise metabolic/signaling pathway, e.g., one miR targets mRNAs of enzymes important for cholesterol synthesis, degradation, and transport. Therefore, changes in the levels of one key miR affect various steps of one pathway, which is thereby promoted or inhibited. This makes miRs potent future diagnostic and even therapeutic tools for personalized medicine. Within this chapter, the most prominent microRNAs involved in lipid metabolism, e.g., miR-27a/b, miR-33/33*, miR-122, miR-144, or miR-223, and their intracellular and extracellular functions will be extensively discussed, in particular focusing on their mechanistic role in the pathophysiology of atherosclerosis. Special emphasis will be given on miR-122, the first microRNA currently in clinical trials for the treatment of hepatitis C and on miR-223, the most abundant miR in lipoprotein particles.

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Section: Micrornas Involvement In Lipid Metabolismmentioning

confidence: 99%

Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis

Novák

Olejníčková

Tkáčová

et al. 2015

Advances in Experimental Medicine and Biology

104

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“…Discovery of endogenous microRNAs (miRs) provides a new way of treating dyslipidemia and associated cardiovascular disease (26,27). MiRs are endogenous gene products of ϳ22 nucleotides.…”

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confidence: 99%

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice

Irani

Pan

Peck

et al. 2016

Journal of Biological Chemistry

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High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe ؊/؊ mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis.Atherosclerosis, hardening of the arteries secondary to lipid deposition, is the major cause of morbidity and mortality in the United States (1-3). High plasma cholesterol levels are a major risk factor for cardiovascular diseases, and their reduction is a national goal (2, 4). Currently, statins are the standard of care. They lower plasma cholesterol by reducing cholesterol synthesis and enhancing the rate of removal of lipoproteins from the plasma. Statins lower plasma cholesterol by 20 -30% and cardiovascular disease mortality by 30 -40% (5-8). Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) 2 inhibitors have emerged as potential new drugs for the treatment of hyperlipidemia (9). PCSK9 binds to LDL receptor and targets it for lysosomal degradation. Thus, inhibition of PCSK9 leads to increased LDL receptor expression, increased clearance of lipoproteins, and decreased plasma LDL cholesterol levels (10 -12). Because both statins and PCSK9 antibodies reduce plasma cholesterol by modulating LDL receptor expression, they are ineffective in homozygous familial hypercholesterolemia subjects with Ͻ2% of the LDL receptor activity (11,13,14). In addition, a significant percentage o...

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“…Another study found miR-126 necessary for endothelial recovery and reported that lesion formation was stimulated by the down regulation of miR-145, playing a role in the differentiation of smooth muscle cells [49]. Macrophages in the atherosclerotic plaques execute inflammatory responses by the phagocytosis of lipoproteins and dead cells [50]. miRNAs control the activity and differentiation of macrophages through various signaling pathways [51].…”

Section: Micro-rnas In Cardiovascular Diseasesmentioning

confidence: 99%

Unknown Aspects of Well-known Cardiovascular Diseases: Identification of Novel miRNA Genes

Çeviker¹,

Bağcı²,

Yazkan³

2016

Ann Clin Anal Med

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ÖzetKodlanmayan küçük ribonükleik asit (miRNA)'lerin bulunması ve işlevlerinin tanımlanmasıyla, RNA'ların canlı yaşamı için çok önemli süreçlerde rol oynadıkları belirlenmiştir. miRNA'larda meydana gelen bozukluklar birçok hastalı-ğa yol açmaktadır. Beklendiği üzere kanserler, nörodejeneratif hastalıklar ve immün yetmezlik gibi hastalıklarla ilişkilendirilmiş ve son yıllarda yeni yapı-lan çalışmalarla kardiyovasküler hastalıklarla olan ilişkilileri gösterilmiştir. Bu miRNA'lar, yeni tedavi yaklaşımlarında hem hedef hem de araç olarak görül-mektedirler. İnsan genomundaki tüm miRNA'ların işlevlerinin aydınlatılmasıy-la yeni tedavi yaklaşımları geliştirilebilecektir. Bu derlemede, miRNA'ların kardiyovasküler hastalıklarla ilişkili olduğu kuvvetli çalışmalarla ispatlanan çeşit-leri, kardiyovasküler hastalıklarla olan ilişkileri, ve tanı-tedavi amaçlı kullanımlarıyla ilgili literatüre dayalı değerlendirme yapılmıştır. Anahtar KelimelerKardiyovasküler Hastalık; Ateroskleroz; Miyokard Enfarktüsü (MI); Mikro RNA

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Role of microRNA-30c in lipid metabolism, adipogenesis, cardiac remodeling and cancer

Cited by 42 publications

References 83 publications

Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis

Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice

Unknown Aspects of Well-known Cardiovascular Diseases: Identification of Novel miRNA Genes

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