ABSTRACT
Abnormal angiogenesis is a critical factor in tumor growth and metastasis, and protein arginine methyltransferase 5 (PRMT5), a prominent type II enzyme, is implicated in various human cancers. However, the precise role of PRMT5 in regulating angiogenesis to promote lung cancer cell metastasis and the underlying molecular mechanisms are not fully understood. Here, we show that PRMT5 is overexpressed in lung cancer cells and tissues, and its expression is triggered by hypoxia. Moreover, inhibiting or silencing PRMT5 disrupts the phosphorylation of the VEGFR/Akt/eNOS angiogenic signaling pathway, NOS activity, and NO production. Additionally, inhibiting PRMT5 activity reduces HIF-1α expression and stability, resulting in the down-regulation of the VEGF/VEGFR signaling pathway. Our findings indicate that PRMT5 promotes lung cancer epithelial-mesenchymal transition (EMT), which might be possibly through controlling the HIF-1α/VEGFR/Akt/eNOS signaling axis. Our study provides compelling evidence of the close association between PRMT5 and angiogenesis/EMT and highlights the potential of targeting PRMT5 activity as a promising therapeutic approach for treating lung cancer with abnormal angiogenesis.
Subject(s)
Lung Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Signal Transduction , Lung Neoplasms/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolismABSTRACT
miRNA-21 (miR-21) is overexpressed in various human cancers. Here, we show that miR-21 is overexpressed in human Non-Small Cell Lung Cancer (NSCLC) and that its up or down-regulation, respectively, increases or decreases cyclin D1 and cyclin E1 expression and coordinately promotes or inhibits proliferation of cancer cells. The perturbations of miR-21 also dramatically reduces or increases epithelial to mesenschymal transition (EMT). We show that regulation of proliferation and EMT are directed by PTEN/Akt/GSK3 beta signaling axis by regulating the expression of invasion markers including E-cadherin, vimentin, snail, slug and beta-catenin. Together, these findings show that miR-21 is a potential target for the development of treatment for NSCLC forms of human lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , MicroRNAs/genetics , Signal Transduction/genetics , A549 Cells , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cyclins/genetics , Cyclins/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
The top emission organic light-emitting devices were fabricated on the multi-layers metal anode with co-doping method in single host system. In experiment, the multilayer Al/Mo/MoO(3) anode on silicon are deposited, systematically analyzed the effect MoO(3) thickness on the reflectance and found the mechanism of the MoO(3) thickness variation to the reflectivity of Al/Mo/MoO(3) on silicon. Experimental results showed that the luminous intensity of blue, green and red appear to change according to the current density increase, and compared with the red intensity, the luminous intensity of blue and green gradually increased. The emission in this host-guest co-doping system is considered to usually involve two emission mechanisms, energy transfer and carrier trapping, and the energy transfer and carrier trapping between the host-guest should be responsible for chromaticity coordinates shift of organic white emitting light devices. In addition, through further study, it is proved the electroluminescence intensity of dopant linearly decrease with the driving voltage applied to the device by theoretical and experimental results.
