摘要：
Zinc finger protein 382 (ZNF382), a member of the Kruppel-associated box zinc finger proteins (KRAB-ZFPs) family, plays critical roles in regulating certain downstream genes expression as a transcription inhibitor. ZNF382 is downregulated in multiple tumors due to hypermethylation of its promoter, to be more specific, methylation of promoter CpG island may contributes to inhibition of gene expression as found in many studies. With application of DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2'-deoxycytidine, hypomethylation of ZNF382 gene may contribute to anti-tumor effects. This review summerized the structure, biological functions, expression and the roles of ZNF382 in multiple cancers, and, expression of ZNF382 regulated by promoter methylation was further discussed to show the possibilities of DNA hypomethylation treatment as a potential treatment in clinical applications.
摘要：
Gastric cancer (GC) is the fifth most common primary malignancy in humans. Rho GDP dissociation inhibitor 2 (RhoGDI2) is overexpressed in multiple cancer types, but the role of RhoGDI2 in GC has not been elucidated. This study aims to determine the level of RhoGDI2 in GC and to confirm the effect of its inhibition or overexpression on GC cell migration, invasion and chemosensitivity. RhoGDI2 level is significantly enhanced in human GC tissue samples in comparison with normal gastric epithelium and corresponding para-cancerous samples. The expression of RhoGDI2 is correlated with clinicopathological parameters and prognosis. Transfection in combination with miRNA targeting of RhoGDI2 in GC cell lines remarkably downregulates GC cell migration and invasion and reduces the mRNA levels of Rac1, Pak1 and LIMK1. The inhibition of RhoGDI2 downregulates GC cell migration and invasion by attenuating the EMT cascade via the Rac1/Pak1/LIMK1 pathway. Knockdown of RhoGDI2 is a potential therapeutic strategy for GC.
摘要：
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an RNA/DNA special binding protein that participates in regulating the expression of related genes, transcription, RNA alternative splicing, translation, posttranslational modification, cell signal transduction, cell movement, interacts with ncRNAs, and induces angiogenesis. Moreover, several cellular functions forcefully indicated that hnRNP K participates in tumorigenesis. Numerous studies indicated hnRNP K is aberrantly elevated in multiple tumors. In addition, hnRNP K abnormal accumulation in cytoplasmic is also associated with poor prognosis. This suggests that hnRNP K may play a role in the development and progression of tumors. However, related studies demonstrated that hnRNP K acts as a tumor suppressor to suppress tumor formation. Therefore, this paper aims to explore the role of hnRNPK in tumors.
摘要：
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 0 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. (C) 2015 Published by Elsevier B.V.
通讯机构：
[Yin, Wei-Dong] U;Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词：
Apolipoprotein E knockout mice;Atherosclerosis;LPL;miR-467b
摘要：
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-alpha), interleukin-6 (IL-6), IL-1 beta 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. (C) 2013 Elsevier Inc. All rights reserved.
摘要：
Background: Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. Methods and results: Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red 0 staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in human THP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated human THP-1 macrophages. Conclusions: MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in human THP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases. (C) 2014 Elsevier B.V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM). All rights reserved.
