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 TGFβ 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.
A total of 238 samples of PM<sub>2.5</sub> and TSP were analyzed to study the characteristics, sources, and formation pathways of aerosol oxalate in Shanghai in four seasons of 2007. The concentrations of oxalate were 0.07–0.41 μg m<sup>−3</sup> in PM<sub>2.5</sub> and 0.10–0.48 μg m<sup>−3</sup> in TSP, respectively. Oxalate displayed a seasonal variation of autumn>summer>winter>spring in both PM<sub>2.5</sub> and TSP and was dominantly present in PM<sub>2.5</sub> in all samples. Correlation between oxalate and K<sup>+</sup> and high ratio of oxalate/K<sup>+</sup> suggested that biomass burning was a secondary source of aerosol oxalate in Shanghai, in addition to urban VOCs sources (vehicular and industrial emissions), especially in autumn. Secondary formation accounted for the majority of aerosol oxalate in Shanghai, which was supported by the high correlation of oxalate with nss-SO<sub>4</sub><sup>2−</sup>, K<sup>+</sup> and NO<sub>3</sub><sup>−</sup>, proceeding from different mechanisms. Relatively high ambient RH together with high cloud cover was found benefiting the secondary formation of aerosol oxalate. The in-cloud process (aqueous-phase oxidation) was proposed to be likely the major formation pathway of aerosol oxalate in Shanghai, which was supported by the high correlation of oxalate with nss-SO<sub>4</sub><sup>2−</sup> and K<sup>+</sup> , dominant residence of oxalate in droplet mode and result of favorable meteorological condition analysis. High correlation of oxalate and NO<sub>3</sub><sup>−</sup> reflected the OH radical involved oxidation chemistry of the two species in the atmosphere and also suggested that gas-particle surface reactions and evaporation-condensation process were both possible secondary formation pathways of aerosol oxalate in coarser particle mode (>1.0 μm). Aerosol oxalate contributed to the haze pollution and visibility degradation of the local environment. As a major water-soluble organic compound in aerosols, concentration of oxalate showed a distinct negative correlation to the atmospheric visibility, which implied that aerosol organic compounds could play an important role in air quality in Shanghai
Purpose: To investigate the eye lens dose reduction by CT scan with organ based tube current modulation (OBTCM) using GPU Monte Carlo code ARCHER‐CT. Methods: 36 X‐ray sources and bowtie filters were placed around the patient head with the projection angle interval of 10° for one rotation of CT scan, each projection was simulated respectively. The voxel eye models with high resolution(0.1mm*0.1mm*0.1mm) were used in the simulation and different tube voltage including 80kVp, 100kVp, 120kVp and 140kVp were taken into consideration. Results: The radiation doses to the eye lens increased with the tube voltage raised from 80kVp to 140kVp, and the dose results from 0° (AP) direction are much higher than those from 180° (PA) direction for all the 4 different tube voltage investigated. This 360° projection dose characteristic enables organ based TCM, which can reduce the eye lens dose by more than 55%. Conclusion: As the eye lens belongs to superficial tissues, its radiation dose to external exposure like CT is direction sensitive, and this characteristic feature makes organ based TCM to be an effective way to reduce the eye lens dose, so more clinical use of this technique were recommended. National Nature Science Foundation of China(No.11475047)
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