Transcription factor c-Myb promotes the invasion of hepatocellular carcinoma cells via increasing osteopontin expression

<p>Abstract</p> <p>Background</p> <p>Specific gene expression is tightly regulated by various transcription factors. Osteopontin (OPN) is a phosphoprotein that mediates hepatocellular carcinoma (HCC) progression and metastasis. However, the mechanism of OPN up-regulation in HCC metastasis remains to be clarified.</p> <p>Methods</p> <p>Oligonucleotide array-based transcription factor assays were applied to compare different activities of transcription factors in two human HCC cell lines with different OPN expression levels. The effects of one selected transcription factor on OPN expression were further evaluated.</p> <p>Results</p> <p>Eleven transcription factors were over-expressed in metastatic HCC cell line HCCLM6 cells whereas twelve transcription factors were down-regulated. Electrophoretic mobility shift assays (EMSA) and reporter gene assays showed that one of up-regulated transcription factors c-Myb could bind the OPN promoter and increase its transcription activity. In addition, small interfering RNA targeting c-Myb could inhibit OPN expression and significantly decrease migration and invasion of HCCLM6 cells <it>in vitro</it>.</p> <p>Conclusion</p> <p>Our data first demonstrate that c-Myb has a functionally important role in the regulation of OPN expression in HCC cells, suggesting that c-Myb might be a new target to control HCC metastasis.</p

2,2-Dimethyl-5-[(pyridin-2-yl­amino)­methyl­idene]-1,3-dioxane-4,6-dione

In the title compound, C12H12N2O4, the dihedral angle between the pyridine and enamine planes is 3.5 (3)°, while the angle between the dioxanedione (seven atoms) and enamine planes is 4.6 (3)°. The dioxane ring approximates an envelope conformation

2,2-Dimethyl-5-[(2-nitro­anilino)methyl­idene]-1,3-dioxane-4,6-dione

The crystal of the title compound, C13H12N2O6, contains a bifurcated intra­molecular hydrogen bond between the N—H group and one of the O atoms from both the nitro group and the dioxane-4,6-dione moiety. In addition, mol­ecules are linked by a series of inter­molecular C—H⋯O secondary inter­actions. The dihedral angles between the benzene ring and the nitro group and the conjugated part of the dioxane-4,6-dione moiety are 19.1 (2) and 17.89 (7)°, respectively

N-Cyclo­hexyl-4-[(2-nitro­anilino)­meth­yl]thio­phene-2-sulfonamide

In the title compound, C17H21N3O4S2, an intra­molecular N—H⋯O hydrogen bond involving the proximate amine and nitro groups is observed. In the crystal, inter­molecular N—H⋯O hydrogen bonds involving the amine and SO2 groups occur. One of the notro O atoms is disordered over two conformations with occupancies of 0.578 (12) and 0.422 (12)

5-(1H-Indol-3-yl­methyl­idene)-2,2-di­methyl-1,3-dioxane-4,6-dione

In the title compound, C15H13NO4, the conjugated double-bond system between the two rings adopts a cis configuration and there is an intra­molecular indole–ketone C—H⋯O inter­action. The indole N—H group forms an inter­molecular hydrogen bond with a ketone O-atom acceptor, giving a chain structure along the ab direction. The O-heterocyclic ring adopts a boat conformation and makes a dihedral angle of 16.72 (6)° with the indole ring system

Analysis of operation performance of three indirect expansion solar assisted air source heat pumps for domestic heating

To achieve the goal set for net-zero emissions of greenhouse gases in the UK by 2050, the domestic heating must be decarbonised. Solar assisted air source heat pumps, integrating solar collector, thermal energy storage tank and heat pump, offers a promising alternative application under the UK weather conditions. Literature review shows that investigations of solar assisted air source heat pumps in the regions like the UK are still insufficient. The serial, parallel and dual-source indirect expansion solar assisted air source heat pumps are modelled and simulated under the weather conditions in London using TRNSYS to investigate the operation performance over a typical year. These three heat pumps are applied to provide space heating and hot water of 300 L per day for a typical single-family house. The simulation results show comparisons of the three systems. The serial type heat pump shows the highest seasonal performance factor of 5.5, but requiring the largest sizes of the solar collector and thermal energy storage tank. The dual-source and parallel type heat pumps show slightly lower seasonal performance factors of 4.4 and 4.5, respectively, requiring smaller sizes of solar collector and thermal energy storage tank. Furthermore, the results show that the air source part contributes to an important proportion of the heat provision and stable operation of the systems. The yearly seasonal performance factor higher than 4.4 achievable by the three heat pumps suggests that they are potentially applied in the regions with relatively lower solar irradiance. The economic analyses indicate that the parallel and dual-source type heat pumps provide good alternatives to replace the gas-boiler heating system

ER-α36, a Novel Variant of ER-α, Mediates Estrogen-Stimulated Proliferation of Endometrial Carcinoma Cells via the PKCδ/ERK Pathway

Recently, a variant of ER-α, ER-α36 was identified and cloned. ER-α36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. The purpose of this study was to investigate the function and the underlying mechanisms of ER-α36 in growth regulation of endometrial Ishikawa cancer cells.The cellular localization of ER-α36 and ER-α66 were determined by immunofluorescence in the Ishikawa cells. Ishikawa endometrial cancer control cells transfected with an empty expression vector, Ishikawa cells with shRNA knockdown of ER-α36 (Ishikawa/RNAiER36) and Ishikawa cells with shRNA knockdown of ER-α66 (Ishikawa/RNAiER66) were treated with E2 and E2-conjugated to bovine serum albumin (E2-BSA, membrane impermeable) in the absence and presence of different kinase inhibitors HBDDE, bisindolylmaleimide, rottlerin, H89 and U0126. The phosphorylation levels of signaling molecules and cyclin D1/cdk4 expression were examined with Western blot analysis and cell growth was monitored with the MTT assay.Immunofluorescence staining of Ishikawa cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and in the cytoplasm, while ER-α66 was predominantly localized in the cell nucleus. Both E2 and E2-BSA rapidly activated PKCδ not PKCα in Ishikawa cells, which could be abrogated by ER-α36 shRNA expression. E2-and E2-BSA-induced ERK phosphorylation required ER-α36 and PKCδ. However, only E2 was able to induce Camp-dependent protein kinase A (PKA) phosphorylation. Furthermore, E2 enhances cyclin D1/cdk4 expression via ER-α36.E2 activates the PKCδ/ERK pathway and enhances cyclin D1/cdk4 expression via the membrane-initiated signaling pathways mediated by ER-α36, suggesting a possible involvement of ER-α36 in E2-dependent growth-promoting effects in endometrial cancer cells

Long-distance transport of sucrose in source leaves promotes sink root growth by the EIN3-SUC2 module

In most plants, sucrose, a major storage sugar, is transported into sink organs to support their growth. This key physiological process is dependent on the function of sucrose transporters. Sucrose export from source tissues is predominantly controlled through the activity of SUCROSE TRANSPORTER 2 (SUC2), required for the loading of sucrose into the phloem of Arabidopsis plants. However, how SUC2 activity is controlled to support root growth remains unclear. Glucose is perceived via the function of HEXOKINASE 1 (HXK1), the only known nuclear glucose sensor. HXK1 negatively regulates the stability of ETHYLENE-INSENSITIVE3 (EIN3), a key ethylene/glucose interaction component. Here we show that HXK1 functions upstream of EIN3 in the regulation of root sink growth mediated by glucose signaling. Furthermore, the transcription factor EIN3 directly inhibits SUC2 activity by binding to the SUC2 promoter, regulating glucose signaling linked to root sink growth. We demonstrate that these molecular components form a HXK1-EIN3-SUC2 module integral to the control of root sink growth. Also, we demonstrate that with increasing age, the HXK1-EIN3-SUC2 module promotes sucrose phloem loading in source tissues thereby elevating sucrose levels in sink roots. As a result, glucose signaling mediated-sink root growth is facilitated. Our findings thus establish a direct molecular link between the HXK1-EIN3-SUC2 module, the source-to sink transport of sucrose and root growth

Glucose and sucrose signaling modules regulate the arabidopsis juvenile-to-adult phase transition

Summary: CINV1, converting sucrose into glucose and fructose, is a key entry of carbon into cellular metabolism, and HXK1 functions as a pivotal sensor for glucose. Exogenous sugars trigger the Arabidopsis juvenile-to-adult phase transition via a miR156A/SPL module. However, the endogenous factors that regulate this process remain unclear. In this study, we show that sucrose specifically induced the PAP1 transcription factor directly and positively controls CINV1 activity. Furthermore, we identify a glucose feed-forward loop (sucrose-CINV1-glucose-HXK1-miR156-SPL9-PAP1-CINV1-glucose) that controls CINV1 activity to convert sucrose into glucose signaling to dynamically control the juvenile-to-adult phase transition. Moreover, PAP1 directly binds to the SPL9 promoter, activating SPL9 expression and triggering the sucrose-signaling-mediated juvenile-to-adult phase transition. Therefore, a glucose-signaling feed-forward loop and a sucrose-signaling pathway synergistically regulate the Arabidopsis juvenile-to-adult phase transition. Collectively, we identify a molecular link between the major photosynthate sucrose, the entry point of carbon into cellular metabolism, and the plant juvenile-to-adult phase transition

Shenfu injection: a review of pharmacological effects on cardiovascular diseases

Shenfu injection (SFI), composed of ginseng and aconite, is a Chinese patent developed from the classic traditional prescription Shenfu Decoction created more than 700 years ago. SFI has been widely used in China for over 30 years for treating cardiovascular diseases. The main components in it include ginsenosides and aconitum alkaloids. In recent years, the role of SFI in the treatment of cardiovascular diseases has attracted much attention. The pharmacological effects and therapeutic applications of SFI in cardiovascular diseases are summarized here, highlighting pharmacological features and potential mechanisms developments, confirming that SFI can play a role in multiple ways and is a promising drug for treating cardiovascular diseases