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MicroRNAs (miRNAs) have been demonstrated to participate in many important cellular processes including radiosensitization. VEGF family, an important regulator of angiogenesis, also plays a crucial role in the regulation of cancer cell radiosensitivity. VEGFR2 mediates the major growth and permeability actions of VEGF in a paracrine/autocrine manner. MiR-200c, at the nexus of epithelial-mesenchymal transition (EMT), is predicted to target VEGFR2. The purpose of this study is to test the hypothesis that regulation of VEGFR2 pathway by miR-200c could modulate the radiosensitivity of cancer cells. Bioinformatic analysis, luciferase reporter assays and biochemical assays were carried out to validate VEGFR2 as a direct target of miR-200c. The radiosensitizing effects of miR-200c on A549 cells were determined by clonogenic assays. The downstream regulating mechanism of miR-200c was explored with western blotting assays, FCM, tube formation assays and migration assays. We identified VEGFR2 as a novel target of miR-200c. The ectopic miR-200c increased the radiosensitivity of A549 while miR-200c down-regulation decreased it. Besides, we proved that miR-200c radiosensitized A549 cells by targeting VEGF-VEGFR2 pathway specifically, thus leading to inhibition of its downstream pro-survival signaling transduction and angiogenesis, and serves as a potential target for radiosensitizition research.

BackgroundFew studies assessed effects of individual and multiple ions simultaneously on metabolic outcomes, due to methodological limitation.Methodology/principal findingsBy combining advanced ionomics and mutual information, a quantifying measurement for mutual dependence between two random variables, we investigated associations of ion modules/networks with overweight/obesity, metabolic syndrome (MetS) and type 2 diabetes (T2DM) in 976 middle-aged Chinese men and women. Fasting plasma ions were measured by inductively coupled plasma mass spectroscopy. Significant ion modules were selected by mutual information to construct disease related ion networks. Plasma copper and phosphorus always ranked the first two among three specific ion networks associated with overweight/obesity, MetS and T2DM. Comparing the ranking of ion individually and in networks, three patterns were observed (1) "Individual ion," such as potassium and chrome, which tends to work alone; (2) "Module ion," such as iron in T2DM, which tends to act in modules/network; and (3) "Module-individual ion," such as copper in overweight/obesity, which seems to work equivalently in either way.ConclusionsIn conclusion, by using the novel approach of the ionomics strategy and the information theory, we observed potential associations of ions individually or as modules/networks with metabolic disorders. Certainly, these findings need to be confirmed in future biological studies.

To study survivin gene expression in APL cells and to explore its correlation with clinical manifestations. PML/RARα and survivin mRNA expression were analysed using RT-PCR. By treatment of ATRA, the survivin mRNA expression in NB4 cells gradually decreased with time and was almost undetectable in the 72th hour. Survivin was expressed in 67% of the 36 APL cases (de novo and relapse patients) with PML/RARα fusion gene expression. However, in 22 cases of remission stage patients without PML/RARα fusion gene expression, survivin was expressed in 36%. The survivin mRNA expression positive rate in de novo and relapse groups, and PML/RARα fusion gene L-type positive groups, was obviously higher than those in remission period groups and was significantly lower than those in acute leukemia groups. In 36 cases of de novo and relapse APL patients, all cases could obtain complete remission, irrespective of the survivin expression. APL patients expressed with survivin mRNA had DIC and serious infection (one patient died). The clinical symptom included slight skin or mucosa bleeding, fever, and asthenic for patients without the survivin mRNA expression. Later, two cases of APL patients with the survivin mRNA expression were treated by ATRA, induction differentiation sign in their peripheral blood and bone marrow figure was not obvious. It was concluded that the survive gene expression was lower in APL than those in any other types of leukemia, thus closely associated with clinical manifestation.