RP5-833A20.1/miR-382-5p/NFIA–Dependent Signal Transduction Pathway Contributes to the Regulation of Cholesterol Homeostasis and Inflammatory Reaction

Abstract

A therosclerosis is the underlying cause of cardiovascular disease (CVD), which is the leading cause of mortality worldwide.1 CVD is initiated by the accumulation of lipids, necrotic cells, and fibrous elements in the neointima of medium and large arteries. 2,3 The primary cells that contribute to atherosclerotic lesion formation are endothelial cells, vascular smooth muscle cells, and macrophages. [4][5][6] Plaque formation results from the infiltration of circulating monocytes in the subendothelial space, where they differentiate into macrophages and subsequently internalize modified lipoproteins and further differentiate into foam cells. 7 Therefore, further clarification of the mechanisms leading to macrophage accumulation is important to prevent plaque rupture and subsequent life-threatening clinical complications, such as myocardial infarction and stroke. See accompanying editorial on page 7The nuclear receptor superfamily is composed of transcription factors that positively and negatively regulate gene expression, which not only influence lipid metabolism at the systemic level but also regulate lipid homeostasis and inflammation in macrophages, endothelial cells, and smooth muscle cells within the arterial walls. 8,9 The nuclear factor I (NFI) family of site-specific DNA-binding proteins are critical regulators of gliogenesis in the developing central nervous system.10,11 NFIA, a member of the NFI family, can modulate DNA replication and transcription through binding to duplex DNA containing the TTGGC motif or 5′-TTGGCN 5 GCCAA-3′ consensus sequence. 12 Many studies have shown that NFIA plays critical roles in specifying glial cell identity and promoting astrocyte differentiation during embryonic development. 10,11 In addition, a recent study demonstrated that NFIA was functionally required for proper adipocyte differentiation and lipid droplet formation. Overexpression of NFIA in 3T3-L1 cells could significantly result in lipid droplet formation without differentiation stimulus. Overexpression of dominantnegative NFIA or small interfering RNA (siRNA)-mediated knockdown of NFIA could markedly inhibit lipid accumulation during differentiation 13 . However, no publication has © 2014 American Heart Association, Inc. Objective-Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear. Approach and Results-Using microarray analysis, we found that long noncoding RNA RP5-833A20.1 expression was upregulated, whereas nuclear factor IA (NFIA) expression was downregulated in human acute monocytic leukemia macrophage-derived foam cells. Moreover, we showed that long noncoding RNA RP5-833A20.1 may decreases NFIA expression by inducing hsa-miR-382-5p expression in vitro. We found that the RP5-833A20.1/hsa-miR-382-5p/NFIA pathway is essenti...

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells

“…Based on these findings, the present study examine the potential roles of lncRNAs in binding to and regulating miRNAs. In our previous study, it was confirmed that hsa-miR-382-5p is involved in regulating the expression of NFIA by RP5-833A20.1 (27). The results of the present study showed that the overexpression of RP5-833A20.1 suppressed the expression of NFIA in U251 cells.…”

“…In our previous study, it was found that RP5-833A20.1 suppressed the expression of NFIA by promoting the expression of miR-382-5p in THP-1 macrophages (27). The present study examined whether RP5-833A20.1 regulates the expression of NFIA by promoting miR-382-5p in U251 cells.…”

“…In our previous study, it was shown that the RP5-833A20.1/miR-382-5p/NFIA pathway is essential for the regulation cardiovascular disease (27). Several studies have shown that NFIA is important in glioma (25,26).…”

“…The RP5-833A20.1 lncRNA is located in intron 2 of the NFIA gene and has an opposite transcription direction to NFIA. Our previous investigations showed that NFIA is important in the progression of atherosclerosis, which is regulated by RP5-833A20.1 (27). However, whether NFIA is targeted by RP5-833A20.1 in glioma remains to be elucidated.…”

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

“…(4) The fact that we observed in vitro for miR-382-3p a negative effect on adipogenic differentiation could be potentially explained by taking into account recent findings published by Hu and colleagues. (88) Although their work was primarily focused on miR-382-5p in the context of cholesterol homeostasis and inflammation, while we studied miR-382-3p, as a byproduct Hu and colleagues experimentally validated nuclear factor IA (NFIA) as a target that is downregulated by miR-382-3p. Interestingly, NFIA was shown by Waki and colleagues (89) to be functionally required for proper adipocyte differentiation and lipid droplet formation.…”