microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

Desgagné, Véronique; Bouchard, Luigi; Guérin, Renée

doi:10.1515/cclm-2016-0575

Cited by 42 publications

(32 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They regulate gene expression by binding to the 3’-untranslated regions (3’-UTR) of mRNAs, leading to the degradation or translation repression of the targeted mRNAs [88–90]. miRNAs have been identified and demonstrated to regulate nearly all cellular processes, i.e., cell cycle, apoptosis, autophagy, differentiation and metabolism [91–93]. The role of miRNAs in lipid metabolism has been extensively reviewed [92–96].…”

Section: Regulation Of Scap/srebps By Micro-rnamentioning

confidence: 99%

SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

Cheng

Guo

2018

CTMC

View full text Add to dashboard Cite

Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavage-activating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.

show abstract

Section: Regulation Of Scap/srebps By Micro-rnamentioning

confidence: 99%

SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

Cheng

Guo

2018

CTMC

View full text Add to dashboard Cite

show abstract

“…Moreover, recent studies indicated that microRNAs (miRNAs) emerge as novel biomarkers and potential therapeutic targets in the treatment of hyperlipidemia and hepatic lipid dysregulation [11]. MiRNAs, which are small noncoding RNAs molecules composed of 19-25 nucleotides, have been implicated in the regulation of a wide spectrum of biological processes through binding to the 3 0 UTR of target genes and further inducing mRNA destabilization and/or translational repression [12].…”

Section: Introductionmentioning

confidence: 99%

Genipin alleviates high‐fat diet‐induced hyperlipidemia and hepatic lipid accumulation in mice via miR‐142a‐5p/SREBP‐1c axis

et al. 2017

View full text Add to dashboard Cite

Hyperlipidemia is a chronic disorder which plays an important role in the development of cardiovascular diseases, type 2 diabetes, atherosclerosis, hypertension, and nonalcoholic fatty liver disease. Genipin (GNP) is a metabolite from genipioside, which is an active component of the traditional Chinese medicine Gardenia jasminoides Ellis, and has been recognized as a beneficial compound against metabolic disorders. However, whether it can correct overnutrition-induced dyslipidemia is still unknown. In this study, the effects of GNP on attenuating hyperlipidemia and hepatic lipid accumulation were investigated using normal and obese mice induced with a high-fat diet (HFD) and primary hepatocytes treated with free fatty acids. We also sought to identify potential targets of GNP to mediate its effects in the liver. We found that obese mice treated with GNP showed a decrease in the body weight, serum lipid levels, as well as hepatic lipid accumulation. Besides, GNP regulated hepatic expression levels of lipid metabolic genes, which are important in maintaining systemic lipid homeostasis. At the molecular level, GNP increased the expression levels of miR-142a-5p, which bound to 3' untranslated region of Srebp-1c, an important regulator of lipogenesis, which thus led to the inhibition of lipogenesis. Collectively, our data demonstrated that GNP effectively antagonized HFD-induced hyperlipidemia and hepatic lipid accumulation in mice. Such effects were achieved by regulating miR-142a-5p/SREBP-1c axis.

show abstract

“…Over recent decades, miRNAs have been proposed as central regulators of lipid and lipoprotein metabolism [43][44][45]. The miR-33 family has attracted attention because of its role in the regulation of genes involved in HDL metabolism, cholesterol efflux, fatty acid oxidation, and bile acid synthesis and secretion [46].…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Affects Lipid Metabolism in Atherosclerosis Via CHOP Activation and Over-Expression of miR-33

Sun

Zhang

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Endoplasmic reticulum (ER) stress is an important event in atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol metabolism via multiple pathways. This study aimed to determine the relationship between ER stress and lipid metabolism and to verify that upregulation of miR-33 is involved in this process. Methods: An atherosclerosis model was established in apolipoprotein E-deficient (ApoE^-/-) mice fed a Western diet, and THP-1 derived macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining were used to quantify the atherosclerotic plaques. 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers associated with ER stress and cholesterol metabolism in atherosclerotic plaques and macrophages were evaluated by real-time PCR and western blotting, respectively. Immunofluorescence was used to observe alterations of ABCA1 localization. Small interfering RNAs were used to knock down CHOP and miR-33 in macrophages to alter CHOP and miR-33 expression. Results: Atherosclerotic lesions and systemic lipid levels were ameliorated after inhibition of ER stress (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress regulated the lipid catabolism of macrophages by promoting cholesterol uptake, inhibiting cholesterol efflux, and modulating the expression of related transporters. CHOP contributed to lipid metabolism disorder following ER stress. Furthermore, over-expression of miR-33 was involved in ER stress that induced lipid metabolism disorder in macrophages. These findings support a model of ER stress induction by oxidized low-density lipoprotein that affects macrophage lipid catabolism disorder. Conclusion: Our data shed new light on the relationship between ER stress and lipid metabolism in vivo and in vitro, and confirm that upregulation of miR-33 is involved in this process. The relationship between ER stress and miR-33 represents a novel target for the treatment of atherosclerosis.

show abstract

microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

Cited by 42 publications

References 193 publications

SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

Genipin alleviates high‐fat diet‐induced hyperlipidemia and hepatic lipid accumulation in mice via miR‐142a‐5p/SREBP‐1c axis

Endoplasmic Reticulum Stress Affects Lipid Metabolism in Atherosclerosis Via CHOP Activation and Over-Expression of miR-33

Contact Info

Product

Resources

About