MicroRNA-27a is a key modulator of cholesterol biosynthesis
Abrar A. Khan,Heena Agarwal,Heena Agarwal,S Santosh Reddy,S Santosh Reddy,Vikas Arige,Bhargavi Natarajan,Vinayak Gupta,Ananthamohan Kalyani,Manoj Kumar Barthwal,Nitish R. Mahapatra +10 more
TLDR
In this paper, the role of microRNAs (miRNAs) in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (Hmgcr) expression was explored.Abstract:
Hypercholesterolemia is a strong predictor of cardiovascular diseases. The 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (Hmgcr) coding for the rate-limiting enzyme in the cholesterol biosynthesis pathway is a crucial regulator of plasma cholesterol levels. However, the posttranscriptional regulation of Hmgcr remains poorly understood. The main objective of this study was to explore the role of microRNAs (miRNAs) in the regulation of Hmgcr expression. Systematic in silico predictions and experimental analyses reveal that miRNA 27a (miR-27a) specifically interacts with the Hmgcr 3' untranslated region in murine and human hepatocytes. Moreover, our data show that Hmgcr expression is inversely correlated with miR-27a levels in various cultured cell lines and in human and rodent tissues. Actinomycin D chase assays and relevant experiments demonstrate that miR-27a regulates Hmgcr by translational attenuation followed by mRNA degradation. Early growth response 1 (Egr1) regulates miR-27a expression under basal and cholesterol-modulated conditions. miR-27a augmentation via tail vein injection of miR-27a mimic in high-cholesterol-diet-fed Apoe -/- mice shows downregulation of hepatic Hmgcr and plasma cholesterol levels. Pathway and gene expression analyses show that miR-27a also targets several other genes (apart from Hmgcr) in the cholesterol biosynthesis pathway. Taken together, miR-27a emerges as a key regulator of cholesterol biosynthesis and has therapeutic potential for the clinical management of hypercholesterolemia.read more
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Role of Cholesterol and Lipid Rafts in Cancer Signaling: A Promising Therapeutic Opportunity?
TL;DR: In this paper, the current understanding of cholesterol homeostasis in normal and cancerous cells, summarizing key findings from recent preclinical and clinical studies that have investigated the role of major players in cholesterol regulation and the organization of lipid rafts, which could represent promising therapeutic targets.
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The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress.
Adam Włodarski,Justyna Strycharz,Adam Wróblewski,Jacek Kasznicki,Józef Drzewoski,Agnieszka Śliwińska +5 more
TL;DR: Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS and its components, and appear to be important epigenetic modifiers in managing the delicate redox balance.
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Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system
TL;DR: In this article , the role of bilirubin in improving atherosclerosis was investigated, and it was shown that bilibrubin can serve as a negative regulator of the development of atherosclerotic plaques in ApoE-deficient mice.
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The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets.
TL;DR: Intervention in cholesterol metabolism may offer a new therapeutic avenue for cancer treatment based on the existing data, and cholesterol homeostasis is identified to be a new key player in cancer pathogenesis.
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Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system
TL;DR: In this paper , the role of bilirubin in improving atherosclerosis was investigated, and it was shown that bilibrubin can serve as a negative regulator of the development of atherosclerotic plaques in ApoE-deficient mice.
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The Genotype-Tissue Expression (GTEx) project
John T. Lonsdale,Jeffrey Thomas,Mike Salvatore,Rebecca Phillips,Edmund Lo,Saboor Shad,Richard Hasz,Gary Walters,Fernando U. Garcia,Nancy Young,Barbara A. Foster,Mike Moser,Ellen Karasik,Bryan Gillard,Kimberley Ramsey,Susan L. Sullivan,Jason Bridge,Harold Magazine,John Syron,Johnelle Fleming,Laura A. Siminoff,Heather M. Traino,Maghboeba Mosavel,Laura Barker,Scott D. Jewell,Daniel C. Rohrer,Dan Maxim,Dana Filkins,Philip Harbach,Eddie Cortadillo,Bree Berghuis,Lisa Turner,Eric Hudson,Kristin Feenstra,Leslie H. Sobin,James A. Robb,Phillip Branton,Greg E. Korzeniewski,Charles Shive,David Tabor,Liqun Qi,Kevin Groch,Sreenath Nampally,Steve Buia,Angela Zimmerman,Anna M. Smith,Robin Burges,Karna Robinson,Kim Valentino,Deborah Bradbury,Mark Cosentino,Norma Diaz-Mayoral,Mary Kennedy,Theresa Engel,Penelope Williams,Kenyon Erickson,Kristin G. Ardlie,Wendy Winckler,Gad Getz,Gad Getz,David S. DeLuca,MacArthur Daniel MacArthur,MacArthur Daniel MacArthur,Manolis Kellis,Alexander Thomson,Taylor Young,Ellen Gelfand,Molly Donovan,Yan Meng,George B. Grant,Deborah C. Mash,Yvonne Marcus,Margaret J. Basile,Jun Liu,Jun Zhu,Zhidong Tu,Nancy J. Cox,Dan L. Nicolae,Eric R. Gamazon,Hae Kyung Im,Anuar Konkashbaev,Jonathan K. Pritchard,Jonathan K. Pritchard,Matthew Stevens,Timothée Flutre,Xiaoquan Wen,Emmanouil T. Dermitzakis,Tuuli Lappalainen,Roderic Guigó,Jean Monlong,Michael Sammeth,Daphne Koller,Alexis Battle,Sara Mostafavi,Mark I. McCarthy,Manual Rivas,Julian Maller,Ivan Rusyn,Andrew B. Nobel,Fred A. Wright,Andrey A. Shabalin,Mike Feolo,Nataliya Sharopova,Anne Sturcke,Justin Paschal,James M. Anderson,Elizabeth L. Wilder,Leslie Derr,Eric D. Green,Jeffery P. Struewing,Gary F. Temple,Simona Volpi,Joy T. Boyer,Elizabeth J. Thomson,Mark S. Guyer,Cathy Ng,Assya Abdallah,Deborah Colantuoni,Thomas R. Insel,Susan E. Koester,Roger Little,Patrick Bender,Thomas Lehner,Yin Yao,Carolyn C. Compton,Jimmie B. Vaught,Sherilyn Sawyer,Nicole C. Lockhart,Joanne P. Demchok,Helen F. Moore +129 more
TL;DR: The Genotype-Tissue Expression (GTEx) project is described, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.