MicroRNA-615-3p decreases apo B expression in human liver cells

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels is associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are...

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Main Authors: Abulaish Ansari, Pradeep Kumar Yadav, Swati Valmiki, Antoine Laine, Antoine Rimbert, Shahidul Islam, Iman Osman, S. Hani Najafi-Shoushtari, M. Mahmood Hussain
Format: Article
Language:English
Published: Elsevier 2024-10-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227524001640
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author Abulaish Ansari
Pradeep Kumar Yadav
Swati Valmiki
Antoine Laine
Antoine Rimbert
Shahidul Islam
Iman Osman
S. Hani Najafi-Shoushtari
M. Mahmood Hussain
author_facet Abulaish Ansari
Pradeep Kumar Yadav
Swati Valmiki
Antoine Laine
Antoine Rimbert
Shahidul Islam
Iman Osman
S. Hani Najafi-Shoushtari
M. Mahmood Hussain
author_sort Abulaish Ansari
collection DOAJ
description Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels is associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce the protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3′-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver-derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion.
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spelling doaj-art-45aab6767b144ede995fcb0e7704e6712025-08-20T02:10:50ZengElsevierJournal of Lipid Research0022-22752024-10-01651010065910.1016/j.jlr.2024.100659MicroRNA-615-3p decreases apo B expression in human liver cellsAbulaish Ansari0Pradeep Kumar Yadav1Swati Valmiki2Antoine Laine3Antoine Rimbert4Shahidul Islam5Iman Osman6S. Hani Najafi-Shoushtari7M. Mahmood Hussain8Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, USA; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA; Department of Research, Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, QatarDepartment of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, USA; Department of Botany, Faculty of Science, University of Allahabad, Prayagraj, IndiaDepartment of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, USANantes Université, CNRS, INSERM, l’institut du thorax, Nantes, FranceNantes Université, CNRS, INSERM, l’institut du thorax, Nantes, FranceDepartment of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, USADepartment of Medicine, New York University Langone Medical Center, New York, NY, USADepartment of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA; Department of Research, Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, QatarDepartment of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, USA; Research Department, New York Harbor Healthcare System, Brooklyn, NY, USA; For correspondence: M. Mahmood HussainPlasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels is associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce the protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3′-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver-derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion.http://www.sciencedirect.com/science/article/pii/S0022227524001640apolipoproteinsapoBlipoproteinsmicroRNAslipidscardiovascular disease
spellingShingle Abulaish Ansari
Pradeep Kumar Yadav
Swati Valmiki
Antoine Laine
Antoine Rimbert
Shahidul Islam
Iman Osman
S. Hani Najafi-Shoushtari
M. Mahmood Hussain
MicroRNA-615-3p decreases apo B expression in human liver cells
Journal of Lipid Research
apolipoproteins
apoB
lipoproteins
microRNAs
lipids
cardiovascular disease
title MicroRNA-615-3p decreases apo B expression in human liver cells
title_full MicroRNA-615-3p decreases apo B expression in human liver cells
title_fullStr MicroRNA-615-3p decreases apo B expression in human liver cells
title_full_unstemmed MicroRNA-615-3p decreases apo B expression in human liver cells
title_short MicroRNA-615-3p decreases apo B expression in human liver cells
title_sort microrna 615 3p decreases apo b expression in human liver cells
topic apolipoproteins
apoB
lipoproteins
microRNAs
lipids
cardiovascular disease
url http://www.sciencedirect.com/science/article/pii/S0022227524001640
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