The Effects of Naringenin on miRNA-mRNA Profiles in HepaRG Cells

Abstract

Naringenin, a natural flavonoid widely found in citrus fruits, has been reported to possess anti-oxidant, anti-inflammatory, and hepatoprotective properties as a natural dietary supplement. However, the regulatory mechanism of naringenin in human liver remains unclear. In the present study, messenger RNA sequencing (mRNA-seq), microRNA sequencing (miRNA-seq), and real-time qPCR were used to distinguish the expression differences between control and naringenin-treated HepaRG cells. We obtained 1037 differentially expressed mRNAs and 234 miRNAs. According to the target prediction and integration analysis in silico, we found 20 potential miRNA-mRNA pairs involved in liver metabolism. This study is the first to provide a perspective of miRNA–mRNA interactions in the regulation of naringenin via an integrated analysis of mRNA-seq and miRNA-seq in HepaRG cells, which further characterizes the nutraceutical value of naringenin as a food additive.

Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women

“…In the present study, we also demonstrated that chronic consumption of GFJ flavanones modulated the expression of 6 miRNAs in PBMCs, revealing for the first time the capacity of these compounds to act on these post-transcriptional regulators in humans. Citrus flavanones have been reported previously to modulate miRNA expression in preclinical models ( 20 , 55 , 56 ), however, data on the impact of these citrus bioactives on miRNA are still limited. MiRNAs have been identified as the important regulators of vascular function, which deregulation seems to contribute to vascular dysfunction and CVD development ( 57 ).…”

Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions

“…Further studies revealed selectively increased let-7g expression in NGN-treated NPC cells. A recent study using human hepatoma HepaRG cells found that NGN suppressed the activity of oncogenic metabolism through the regulation of miRNA-targeted mRNA expression inhibiting PI3K–Akt signaling [ 62 ]. The reported evidence indicates that the expression of has-miR-1306-5p, has-miR-627-3p, has-miR-194-3p, has-miR-676-3p, has-miR-6837-5p, has-miR-429, has-miR-100-3p, has-miR-194-5p, has-miR-519a-3p, has-miR-7-5p, and has-miR-200a-5p was involved in the attenuation of the PI3K–Akt signaling pathway of HepaRG cells by NGN [ 62 ].…”

“…A recent study using human hepatoma HepaRG cells found that NGN suppressed the activity of oncogenic metabolism through the regulation of miRNA-targeted mRNA expression inhibiting PI3K–Akt signaling [ 62 ]. The reported evidence indicates that the expression of has-miR-1306-5p, has-miR-627-3p, has-miR-194-3p, has-miR-676-3p, has-miR-6837-5p, has-miR-429, has-miR-100-3p, has-miR-194-5p, has-miR-519a-3p, has-miR-7-5p, and has-miR-200a-5p was involved in the attenuation of the PI3K–Akt signaling pathway of HepaRG cells by NGN [ 62 ]. The involvement of NGN-induced miRNAs in the negative regulation of PI3K–Akt-mediated anti-oxidative stress and ameliorative metabolism was postulated to be associated with the down-regulation of platelet-derived growth factor receptor β, phosphoenolpyruvate carboxykinase 1, cAMP-responsive element-binding protein 3 like 1, and nuclear factor kappa B mRNA expression targeted by has-miR-1306-5p or has-miR-627-3p [ 62 ].…”

“…The reported evidence indicates that the expression of has-miR-1306-5p, has-miR-627-3p, has-miR-194-3p, has-miR-676-3p, has-miR-6837-5p, has-miR-429, has-miR-100-3p, has-miR-194-5p, has-miR-519a-3p, has-miR-7-5p, and has-miR-200a-5p was involved in the attenuation of the PI3K–Akt signaling pathway of HepaRG cells by NGN [ 62 ]. The involvement of NGN-induced miRNAs in the negative regulation of PI3K–Akt-mediated anti-oxidative stress and ameliorative metabolism was postulated to be associated with the down-regulation of platelet-derived growth factor receptor β, phosphoenolpyruvate carboxykinase 1, cAMP-responsive element-binding protein 3 like 1, and nuclear factor kappa B mRNA expression targeted by has-miR-1306-5p or has-miR-627-3p [ 62 ]. However, this observation is inconsistent with our model of the upregulation of let-7g by NGN-attenuated KRAS–PI3K–Rac1–Akt axis metabolic functions, probably because the study cited used a hepatoma cell that conferred the cell-type specificity of miRNA expression to post-translational regulation of the expression of PI3K–Akt-regulated mRNAs involved in metabolism.…”