β-ionone modulates the expression of miRNAs and genes involved in the metastatic phenotype of microdissected persistent preneoplastic lesions in rats submitted to hepatocarcinogenesis

Abstract

MicroRNAs (miRNAs) are post-transcriptional gene expression regulators which expression is frequently altered in hepatocellular carcinoma (HCC). β-ionone (βI) is noted for its ability to inhibit persistent preneoplastic lesions (pPNLs) in liver rats. We evaluated the expression of miRNAs involved in carcinogenesis and possible targets modulated by βI, in pPNLs and surrounding of microdissected tissues. Rats subjected to resistant hepatocyte model were treated during promotion stage with βI (16 mg/100 g body weight) or corn oil (CO; 0.25 mL/100 g body weight; controls). Five animals receive no treatment (NT). In CO group, 38 and 29 miRNAs showed reduced expression relative to NT (P < 0.05) in pPNLs and surrounding, respectively. No miRNAs showed increased expression in surrounding of the CO compared to NT group; however, 30 miRNAs showed increased expression (P ≤ 0.05) in pPNLs of the CO group. There was no difference between βI and CO groups (P > 0.05) in the expression of miRNAs in surrounding. In pPNLs βI increased expression of miR-122 and miR-34a (P ≤ 0.05) and reduced of Igf2 (P ≤ 0.05), target of the latter, compared to CO. Additionally, βI decreased the expression of miR-181c and its target Gdf2 (P ≤ 0.05). βI reduced the expression of miR-181b and miR-708 (P ≤ 0.05) and increased the expression of their respective target mRNAs Timp3 and Mtss1 (P ≤ 0.05), relative to CO group. Modulation of miRNAs target genes by βI was confirmed in vitro. βI is a promising chemopreventive agent in the initial stages of hepatocarcinogenesis, as it modulates the expression of the miRNAs and target genes that can alter the metastatic phenotype of HCC. © 2016 Wiley Periodicals, Inc.

Science and Healthy Meals in the World: Nutritional Epigenomics and Nutrigenetics of the Mediterranean Diet

“…A recent on-topic study reported interesting nutrigenomic data regarding the miRNA and histone deacetylase modulation ability of some of these foods and drinks peculiar to these countries with no corresponding examples in the MD. The largely used corn, for example, in the form of corn oil induces a differential profile of the expression of tens of miRNAs related to carcinogenesis in the micro dissected liver of rats [136]. Moreover, the kaempferol, contained in grapes, green tea, and potatoes; the resveratrol of grapes, red wine, blueberries, and peanuts; the sinapinic acid in wine and vinegar; the diallyl disulfide of garlic; and the zerumbone of ginger have recently been considered as "natural HDAC inhibitors" [137] and show an in vitro anti-mitotic effect by regulating miRNAs involved in tumor suppression [138].…”

Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

“…In order to confirm the exogenous miR-708 is functional in cells, c-kit(+) CSCs/CPCs were transfected with miR-708 mimics. After 24 h, RNA was isolated and gene expression was analyzed for predicted target genes including PPARα (peroxisome proliferator-activated receptor alpha) which has not been reported yet, and N-Ras (N-Rasproto-oncogene) and Mtss1 (metastasissuppressor 1) which have been reported to be two target genes of miR-708 in rat [ 20 , 21 ]. As shown in Figure 4 A,B, rat PPARα mRNA has one binding site to miR-708, which is highly conserved between species.…”

miR-708-5p: a microRNA with emerging roles in cancer

“…Contrary to previous studies, there is evidence for miR-708-5p to function as an oncogenic miRNA in HCC. Researchers showed that miR-708-5p was overexpressed in persistent preneoplastic liver lesions (pPNLs) compared to surrounding normal liver tissue in rats [ 149 ]. Treatment with β-Ionone, a suppressor of pPNL growth, decreased miR-708-5p levels [ 149 ].…”

“…Researchers showed that miR-708-5p was overexpressed in persistent preneoplastic liver lesions (pPNLs) compared to surrounding normal liver tissue in rats [ 149 ]. Treatment with β-Ionone, a suppressor of pPNL growth, decreased miR-708-5p levels [ 149 ]. miR-708-5p expression also negatively correlated with two tumor suppressors, metalloproteinase inhibitor 3 (Timp3) and metastasis suppressor protein 1 (Mtss1) levels, leading the authors to conclude miR-708-5p acts as a transformative promoter in liver cells [ 149 ].…”

“…Treatment with β-Ionone, a suppressor of pPNL growth, decreased miR-708-5p levels [ 149 ]. miR-708-5p expression also negatively correlated with two tumor suppressors, metalloproteinase inhibitor 3 (Timp3) and metastasis suppressor protein 1 (Mtss1) levels, leading the authors to conclude miR-708-5p acts as a transformative promoter in liver cells [ 149 ]. This conclusion is oversimplified, as both Timp3 and Mtss1 do not always act as tumor suppressors in HCC.…”