Genetic and molecular characterization of determinant of six-rowed spike of barley carrying vrs1.a4.

KEY MESSAGE: Decisive role of reduced vrs1 transcript abundance in six-rowed spike of barley carrying vrs1.a4 was genetically proved and its potential causes were preliminarily analyzed. Six-rowed spike 1 (vrs1) is the major determinant of the six-rowed spike phenotype of barley (Hordeum vulgare L.). Alleles of Vrs1 have been extensively investigated. Allele vrs1.a4 in six-rowed barley is unique in that it has the same coding sequence as Vrs1.b4 in two-rowed barley. The determinant of row-type in vrs1.a4 carriers has not been experimentally identified. Here, we identified Vrs1.b4 in two-rowed accessions and vrs1.a4 in six-rowed accessions from the Qinghai-Tibet Plateau at high frequency. Genetic analyses revealed a single nuclear gene accounting for row-type alteration in these accessions. Physical mapping identified a 0.08-cM (~ 554-kb) target interval on chromosome 2H, wherein Vrs1 was the most likely candidate gene. Further analysis of Vrs1 expression in offspring of the mapping populations or different Vrs1.b4 and vrs1.a4 lines confirmed that downregulated expression of vrs1.a4 causes six-rowed spike. Regulatory sequence analysis found a single 'TA' dinucleotide deletion in vrs1.a4 carriers within a 'TA' tandem-repeat-enriched region ~ 1 kb upstream of the coding region. DNA methylation levels did not correspond to the expression difference and therefore did not affect Vrs1 expression. More evidence is needed to verify the causal link between the 'TA' deletion and the downregulated Vrs1 expression and hence the six-rowed spike phenotype.

circMAN1A2 could serve as a novel serum biomarker for malignant tumors.

Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real-time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.

Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages.

OBJECTIVE: Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages. METHODS AND RESULTS: Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively. CONCLUSION: Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.

The effects of miR-467b on lipoprotein lipase (LPL) expression, pro-inflammatory cytokine, lipid levels and atherosclerotic lesions in apolipoprotein E knockout mice.

Atherosclerosis is a lipid disorder disease characterized by chronic blood vessel wall inflammation driven by the subendothelial accumulation of macrophages. Studies have shown that lipoprotein lipase (LPL) participates in lipid metabolism, but it is not yet known whether post-transcriptional regulation of LPL gene expression by microRNAs (miRNAs) occurs in vivo. Here, we tested that miR-467b provides protection against atherosclerosis by regulating the target gene LPL which leads to reductions in LPL expression, lipid accumulation, progression of atherosclerosis and production of inflammatory cytokines in apolipoprotein E knockout (apoE(-/-)) mice. Treatment of apoE(-/-) mice with intra-peritoneal injection of miR-467b agomir led to decreased blood plasma levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1ß and monocyte chemotactic protein-1 (MCP-1). Using Western blots and real time PCR, we determined that LPL expression in aorta and abdominal cavity macrophages were significantly down-regulated in the miR-467b agomir group. Furthermore, systemic treatment with miR-467b antagomir accelerated the progression of atherosclerosis in the aorta of apoE(-/-) mice. The present study showed that miR-467b protects apoE(-/-) mice from atherosclerosis by reducing lipid accumulation and inflammatory cytokine secretion via downregulation of LPL expression. Therefore, targeting miR-467b may offer a promising strategy to treat atherosclerotic vascular disease.

Growth differentiation factor-15 induces expression of ATP-binding cassette transporter A1 through PI3-K/PKCζ/SP1 pathway in THP-1 macrophages.

OBJECTIVE: The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase Cζ (PKCζ)/specificity protein 1 (SP1) pathway in THP-1 macrophages. METHODS AND RESULTS: We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKCζ and SP1, respectively, suggesting the potential roles of PI3K, PKCζ and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKCζ and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation. CONCLUSION: Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKCζ/SP1 signaling pathway and enhancing cholesterol efflux.

Interleukin-27 inhibits foam cell formation by promoting macrophage ABCA1 expression through JAK2/STAT3 pathway.

The purpose of this study is to determine whether IL-27 regulates macrophage ABCA1 expression, foam cell formation, and also explore the underlying mechanisms. Here, we revealed that IL-27 decreased lipid accumulation in THP-1 derived macrophages through markedly enhancing cholesterol efflux and increasing ABCA1 expression at both protein and mRNA levels. Our study further demonstrated that IL-27 increased ABCA1 level via activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of Janus kinase 2, (JAK2)/STAT3 suppressed the stimulatory effects of IL-27 on ABCA1 expression. The present study concluded that IL-27 reduces lipid accumulation of foam cell by upregulating ABCA1 expression via JAK2/STAT3. Therefore, targeting IL-27 may offer a promising strategy to treat atherosclerotic vascular disease.

[Role of apolipoprotein AI on nascent high-density lipoprotein particle formation].

Apolipoprotein AI (apoA-I) is the major protein component of high-density lipoprotein (HDL), and apoA-I can stabilize the structure of HDL. Whereas the amphipathic alpha-helix is the structural motif for apoA-I to complete the corresponding functionality. In the lipid-free state, the N-terminal of apoA-I molecule is a dynamic four-helix bundle structure, most amino acid residues of the C-terminal domain is the formation of a disordered structure, which is the initial domain that mediates bingding to phospholipid surface. Two molecules of apoA-I are arranged in an anti-parallel, double-belt conformation around the surface of the discoidal HDL particles. However, the apoA-I molecule forms a trefoil scaffold structure, which can adapt to the surface of spherical HDL particles. ATP-binding cassette transporter A1 (ABCA1) can mediate phospholipid and cholesterol efflux from intracellular and interact with apoA-I to generate nascent HDL particles. Overall, apoA-I and HDL as an anti-atherosclerotic effect of primary target, we focus on the molecular structure of apoA-I, which determines the structure and function of different size of HDL particles, as well as the conformational changes after interaction with lipids, in order to learn more about the relationship of apolipoprotein and lipids metabolism against atherosclerosis.

Tertiary-butylhydroquinone upregulates expression of ATP-binding cassette transporter A1 via nuclear factor E2-related factor 2/heme oxygenase-1 signaling in THP-1 macrophage-derived foam cells.

BACKGROUND: Tert-butylhydroquinone (tBHQ), a synthetic phenolic antioxidant, is commonly used as a food preservative because of its potent antilipid peroxidation activity. Several lines of evidence have demonstrated that dietary supplementation with antioxidants has an antiatherogenic function through reducing cholesterol uptake or promoting reverse cholesterol transport. In this study, we investigated whether tBHQ affects expression of ATP-binding cassette transporter A1 (ABCA1) and the potential subsequent effect on cellular cholesterol homeostasis. METHODS AND RESULTS: tBHQ increased ABCA1 protein levels and markedly enhanced cholesterol efflux from THP-1 macrophage-derived foam cells. Furthermore, tBHQ reduced calpain-mediated ABCA1 proteolysis via activation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Inhibition of HO-1 with a pharmacological inhibitor or siRNA and knockdown of Nrf2 suppressed the stimulatory effects of tBHQ on ABCA1 expression and calpain activity. CONCLUSIONS: Nrf2/HO-1 signaling is required for the regulation by tBHQ of ABCA1 expression and cholesterol efflux in macrophage-derived foam cells and an antiatherogenic role of tBHQ is suggested.

[Research advances of the biliary and nonbiliary pathways to reverse cholesterol transport].

Plasma cholesterol levels are the major risk factor for atherosclerosis (AS) and coronary heart disease (CHD). Biliary pathway to reverse cholesterol transport (RCT) is the process that cholesterol in peripheral tissue and macrophages is transported to liver by lipoprotion, then secreted into the bile and finally excreted through feces. According to a large number of studies, there is nonbiliary pathway to RCT to clear excess cholesterol in the body, apart from the biliary pathway to RCT. This review focuses on the current views on the different pathways to RCT, and the regulation on the RCT of the relevant transports, lipoprotion, receptor and so on, aiming at providing new theoretical evidence and acting targets for the treatment of cholelithiasis and AS related disease.

Retraction notice to "Betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via PKC/ERK/c-Fos pathways in RAW264.7 macrophages" [Biochimie 119C (2015) 192-203].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns raised by Dr. Sander Kersten in PubPeer pointed out that Figs. 6.1B and 6.2B of this paper were different figures but the legends and Western blots were identical; the quantification was also seen to be different between the two figures. Shortly afterwards, the authors asked to publish a corrigendum for part B of Fig. 6.1, including images of western blots and associated bar plots. Subsequently, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Fig. 2 E, 6.2 B, 5 A and and 6.2 D, as shown by the reuse of several western blot bands with approximately 180° rotation in each case. After raising the complaint with the authors, the corresponding author agreed that the paper should be retracted. The authors apologise to the readers of the journal.

[A follow-up of the survival and medical factors responsible for the termination of treatment in very or extremely low birth weight infants].

OBJECTIVE: To study the outcomes of very or extremely low birth weight (VLBW/ELBW) infants born between 2000 and 2008 in a single NICU and the medical factors associated with the termination of treatment in some infants. METHODS: In this case control study, the clinical data of 148 VLBW/ELBW infants were retrospectively studied and the surviving infants were followed up. Both univariate analysis and multivariate logistic regression analysis were used to investigate the medical factors associated with terminating treatment in infants. RESULTS: Twenty infants (13.5%) failed to respond to the therapy and died in the hospital. Three infants (2.0%) died after discharge. Nineteen infants (12.8%) did not receive treatment due to decision of the guardian and died. Thirty infants (20.3%) were not followed up after discharge. Seventy-six infants (51.4%) survived, including 47 healthy infants, 2 cases of congenital diseases and 27 cases with poor prognosis. Multivariate logistic regression analysis showed there were 2 significant factors associated with terminating treatment: neonatal respiratory distress syndrome (P=0.030, OR=11.396, 95%CI 1.-102.701) and hospitalization periods (the year 2004-2006) (P=0.039, OR=9.869, 95%CI 1.118-87.140). CONCLUSIONS: The survival status of VLBW and ELBW infants needs to be improved. It is important to decrease the incidence of neonatal respiratory distress syndrome for decreasing the proportion of terminating treatment in the infants.

Targeting EphA2 in cancer.

Eph receptors and the corresponding Eph receptor-interacting (ephrin) ligands jointly constitute a critical cell signaling network that has multiple functions. The tyrosine kinase EphA2, which belongs to the family of Eph receptors, is highly produced in tumor tissues, while found at relatively low levels in most normal adult tissues, indicating its potential application in cancer treatment. After 30 years of investigation, a large amount of data regarding EphA2 functions have been compiled. Meanwhile, several compounds targeting EphA2 have been evaluated and tested in clinical studies, albeit with limited clinical success. The present review briefly describes the contribution of EphA2-ephrin A1 signaling axis to carcinogenesis. In addition, the roles of EphA2 in resistance to molecular-targeted agents were examined. In particular, we focused on EphA2's potential as a target for cancer treatment to provide insights into the application of EphA2 targeting in anticancer strategies. Overall, EphA2 represents a potential target for treating malignant tumors.

Two sequential surgeries in infant with multiple floor of the mouth dermoid cysts: A case report.

BACKGROUND: Multiple intraoral dermoid cysts of large magnitude generally appear in the second or third decade of life. They are rare in infants and are usually solitary. In this case, a large mass was identified in utero during prenatal exams. CASE SUMMARY: We introduce a rare case on multiple dermoid cysts in the floor of the mouth of an infant who underwent two surgeries for this. Preoperative magnetic resonance imaging confirmed a large well-circumscribed cystic lesion that originated at the former midline region in the floor of the mouth in which a suspicious lesion of minute size was likely compressed by the bulkier mass and overlooked. Therefore, the infant underwent two surgeries by an intraoral approach within 9 mo. At 5 mo after the second operation, a routine follow-up ultrasound showed evidence of an additional cyst. No further surgery was planned because the tumor had no immediate effect. CONCLUSION: This report demonstrates the importance of carefully analyzing preoperative imaging to avoid multiple operations for a seemingly isolated oral cyst.

Cloning and characterization of the putative AFAP1-AS1 promoter region.

Actin filament-associated protein 1-antisense RNA1 (AFAP1-AS1), a cancer-related long non-coding RNA, has been found to be upregulated in multiple types of cancers. AFAP1-AS1 is important for the initiation, progression and poor prognosis of many cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism underlying the regulation of AFAP1-AS1 expression is not well-understood. In our study, the potential promoter region of AFAP1-AS1 was predicted by comprehensive bioinformatics analysis. Moreover, promoter deletion analysis identified the sequence between positions -359 and -28 bp as the minimal promoter region of AFAP1-AS1. The ChIP assay results indicate that the AFAP1-AS1 promoter is responsive to the transcription factor c-Myc, which can promote high AFAP1-AS1 expression. This study is the first to clone and characterize the AFAP1-AS1 promoter region. Our findings will help to better understand the underlying mechanism of high AFAP1-AS1 expression in tumorigenesis and to develop new strategies for therapeutic high expression of AFAP1-AS1 in NPC.

The role of exosomal non-coding RNAs in cancer metastasis.

An increasing number of studies has confirmed that many cells can secrete vesicles or exosomes in eukaryotes, which contain important nucleic acids, proteins and lipids and play important roles in cell communication and tumor metastasis. This paper summarizes the comprehensive function of exosomal non-coding RNAs. Although some studies have shown that exosomes mediate tumor signal transduction, the functional mechanism of the tumor metastasis remains to be elucidated. In this paper, we reviewed the role of exosomal non-coding RNAs in mediating cancer metastasis in the tumor microenvironment to provide new ideas for the study of tumor pathophysiology.

Histone Methyltransferase Enhancer of Zeste Homolog 2-Mediated ABCA1 Promoter DNA Methylation Contributes to the Progression of Atherosclerosis.

ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.

Betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via the PKC/ERK/c-Fos pathway in RAW264.7 macrophages.

BACKGROUND: Atherosclerosis is a major cause of coronary artery disease, which is characterized by cellular lipid accumulation. Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism. Studies have shown that macrophage-derived LPL exhibits proatherogenic properties, and plays a major role in lipid accumulation in macrophages. Evidence suggests that oxidative stress can effectively enhance macrophage LPL production. Betulinic acid (BA) is a pentacyclic lupane triterpene with a potent antioxidant activity. In this study, we investigated whether BA affects the expression of macrophage LPL and how it regulates cellular lipid accumulation. METHODS AND RESULTS: We revealed that BA downregulated H2O2-simulated macrophage LPL protein, mRNA levels and its activity in both concentration- and time-dependent manners. Furthermore, BA decreased LPL-involved total cholesterol and triglyceride levels in macrophages. In addition, cellular lipid staining by Oil Red O showed that BA decreased cellular lipid droplet deposition. Next, we confirmed that pretreatment with BA decreased H2O2-induced production of intracellular reactive oxygen species in a concentration-dependent manner. Further studies demonstrated that BA inhibited H2O2-induced membrane translocation of PKC, phosphorylation of ERK1/2 and c-Fos. Finally, the induction of LPL production and activity by H2O2 was abolished by BA, inhibition of PKC or ERK or depletion c-Fos, respectively. CONCLUSIONS: BA, through its role of antioxidant activity, attenuated macrophage-derived LPL expression and activity induced by oxidative stress, and effectively reduced cellular lipid accumulation, likely through inhibition of the pathways involving PKC, ERK and c-Fos. These effects of BA may contribute to its mitigation of atherosclerosis and help develop BA as a therapeutic compound in treatment of atherosclerosis.

Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1.

RATIONALE: Diosgenin (Dgn), a structural analogue of cholesterol, has been reported to have the hypolipidemic and antiatherogenic properties, but the underlying mechanisms are not fully understood. Given the key roles of macrophages in cholesterol metabolism and atherogenesis, it is critical to investigate macrophage cholesterol efflux and development of atherosclerotic lesion after Dgn treatment. OBJECTIVE: This study was designed to evaluate the potential effects of Dgn on macrophage cholesterol metabolism and the development of aortic atherosclerosis, and to explore its underlying mechanisms. METHODS AND RESULTS: Dgn significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) protein, but didn't affect liver X receptor α levels in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by western blotting. The miR-19b levels were markedly down-regulated in Dgn-treated THP-1 macrophages/MPM-derived foam cells. Cholesterol transport assays revealed that treatment with Dgn alone or together with miR-19b inhibitor notably enhanced ABCA1-dependent cholesterol efflux, resulting in the reduced levels of total cholesterol, free cholesterol and cholesterol ester as determined by high-performance liquid chromatography. The fecal 3H-sterol originating from cholesterol-laden MPMs was increased in apolipoprotein E knockout mice treated with Dgn or both Dgn and antagomiR-19b. Treatment with Dgn alone or together with antagomiR-19b elevated plasma high-density lipoprotein levels, but reduced plasma low-density lipoprotein levels. Accordingly, aortic lipid deposition and plaque area were reduced, and collagen content and ABCA1 expression were increased in mice treated with Dgn alone or together with antagomiR-19b. However, miR-19b overexpression abrogated the lipid-lowering and atheroprotective effects induced by Dgn. CONCLUSION: The present study demonstrates that Dgn enhances ABCA1-dependent cholesterol efflux and inhibits aortic atherosclerosis progression by suppressing macrophage miR-19b expression.

MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages.

RATIONALE: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. OBJECTIVE: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. METHODS AND RESULTS: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. CONCLUSION: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1.