miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27(kip1).

MicroRNAs (miRNAs) are increasingly implicated in regulating tumor malignance through their capacity to coordinately repress expression of tumor-related genes. Here, we show that overexpression of miR-194 in lung cancer cell lines, results in suppressing metastasis of lung cancer cells, while inhibiting its expression through 'miRNA sponge' promotes the cancer cells to metastasize. miR-194 expression is also found to be in strongly negative association with metastasis in clinical specimens of non-small cell lung cancer. We demonstrate that miR-194 directly targets both BMP1 and p27(kip1). The resulting downregulation of BMP1 leads to suppression of TGFß activity and, thus, to downregulation of the expression of key oncogenic genes (matrix metalloproteinases MMP2 and MMP9). This leads, in turn, to decreased tumor invasion. In addition, the miRNA-194-induced suppression of p27(kip1) activates the RhoA pathway, producing enhanced development of actin stress fibers and impaired migration of cancer cells. These findings reveal two structurally independent but functionally linked branches of the regulatory and signaling pathway that together provide a bridge between the metastasis-depressing miRNA and the key genes that govern the malignancy of lung cancers.

Why do essential proteins tend to be clustered in the yeast interactome network?

Recently, the debate on the centrality-lethality rule is resolved by the "second-generation" high-throughput Y2H data from the yeast interactome network, which suggests no significant correlation between the degree of connectedness and essentiality of proteins. However, it is still not clear why essential proteins strongly tend to interact with each other. Previously, the concept of essential protein-protein interactions was proposed to explain the mechanism underlying the clustering of essential proteins. In this article we show that 67 to 75% of the excessive interactions between essential proteins (IBEPs) in the yeast interactome network can be attributed to interactions within protein complexes characterised by the same deletion phenotype for subunits within the complex. Furthermore, 20 to 78% of the excess in IBEPs are caused by the strongly modular structure of the network and by variation in protein essentiality among modules. Not only do proteins function as an interactive network in cellular processes, but furthermore, many proteins do not take part in the network alone, but integrate into protein complexes and many functionally related complexes integrate into modules. So, the local structure of protein complexes as both functional and structural modules are the main contributory factors in the clustering of essential proteins.

The effects of selected air pollutants on clearance of titanic oxide particles from the lungs of rats.

A procedure utilizing the lung clearance kinetics of titanic oxide (TiO2) particles was used to determine the effects of inhaled sulphur dioxide (SO2) and nitrogen oxides (NO x) on particle clearance. The procedure is reproducible and mainly tests clearance mechanisms involving alveolar macrophages and the mucociliary transport system at the alveolobronchial clearance pathway. At low SO2 or NOx exposures enhanced particle clearance was observed. Lung clearance was depressed at 15 and 24 ppm of NO2 after 22 exposures as well as at 20 ppm of SO2 after 11 exposures, and also at 1 ppm of SO2 after 25 exposures. Dose-response curves for the SO2 and NOx exposures showed differences explainable by the routes by which these gases reach the alveolar macrophages.

The effect of aerosol charge on the deposition and clearance of TiO2 particles in rats.

A titanium dioxide aerosol when generated by a Wright dust feed will have a higher electrostatic charge by a factor of 5.5 than one which has been discharged by a bipolar ion field produced by a 7.5 mCi 85Kr source. The deposition of particles in the lung of rats was lower by approximately 21% when an aerosol discharger was used. Particle clearance from the lung alveoli was not affected by the use of the discharger.

Effects in the liver of methylene chloride inhaled alone and with ethyl alcohol.

When high concentrations of methylene chloride in combination with high concentrations of ethanol were inhaled for one day by guinea pigs, the extent of the hepatic damage induced suggested an antagonism between the effects of the two agents. However, exposure for five days to approximately 500 ppm of methylene chloride plus high concentrations of ethanol suggested ethanol may potentiate the effects of methylene chloride.