Portulaca oleracea L. Extract Regulates Hepatic Cholesterol Metabolism via the AMPK/MicroRNA-33/34a Pathway in Rats Fed a High-Cholesterol Diet.

This study examined the effect of extruded Portulaca oleracea L. extract (PE) in rats fed a high-cholesterol diet through the AMP-activated protein kinase (AMPK) and microRNA (miR)-33/34a pathway. Sprague-Dawley rats were randomized into three groups and fed either a standard diet (SD), a high-cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), or an HC diet containing 0.8% PE for 4 weeks. PE supplementation improved serum, liver, and fecal lipid profiles. PE upregulated the expression of genes involved in cholesterol efflux and bile acids' synthesis such as liver X receptor alpha (LXRα), ATP-binding cassette subfamily G5/G8 (ABCG5/8), and cholesterol 7 alpha-hydroxylase (CYP7A1), and downregulated farnesoid X receptor (FXR) in the liver. In addition, hepatic gene expression levels of apolipoprotein A-l (apoA-1), paraoxonase 1 (PON1), ATP-binding cassette subfamily A1/G1 (ABCA1/G1), lecithin-cholesterol acyltransferase (LCAT), and scavenger receptor class B type 1 (SR-B1), which are related to serum high-density lipoprotein cholesterol metabolism, were upregulated by PE. Furthermore, hepatic AMPK activity in the PE group was higher than in the HC group, and miR-33/34a expression levels were suppressed. These results suggest that PE improves the cholesterol metabolism by modulating AMPK activation and miR-33/34a expression in the liver.

STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell.

Ets-1 is a cellular homologue of the product of the viral ets oncogene of the E26 virus, and it functions as a tissue-specific transcription factor. It plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. Ets-1 controls the expression of critical genes involved in these processes by binding to ets binding sites present in the transcriptional regulatory regions. Here, we transiently overexpressed Ets-1 in MCF-7 and comprehensively searched for potential downstream targets of Ets-1 by cDNA microarray analysis. The expressions of several interferon-related genes including STAT1 and Nmi were augmented by the overexpression of Ets-1. RT-PCR and Western blotting confirmed the increase in the levels of STAT1 and Nmi mRNA and protein. In contrast, Ets-1 siRNA decreased the expression of STAT1 and Nmi proteins. As in our transient transfection experiments, stable overexpression of Ets-1, also increased the protein expression of STAT1 and Nmi in MCF-7 cells. Taken together, our results indicate that STAT1 and Nmi are downstream targets of Ets-1 in MCF-7 human breast cancer cells.