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ANG

Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1alpha signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1alpha. Blockage of HIF-1alpha signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1alpha and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1alpha signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1alpha signaling. It provides molecular evidence for potential therapy strategies of treating CNV.CI - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Squamous cell carcinoma of the lung is one of the most aggressive cancers, and its aggressiveness is in part due to its intrinsic high rate of metastasis. Moreover, the process of epithelial-mesenchymal transition (EMT) appears to be involved in these neoplastic processes. Furthermore, EMT-type cells share many biological characteristics with the function of angiogenin (ANG) in squamous cell lung carcinoma. We conducted immunohistochemical analysis to detect the expression of ANG, E-cadherin, vimentin, N-cadherin, beta-catenin and TGF-beta1 in 60 cases of squamous cell lung carcinoma tissues. Western blot analysis was adopted to detect the protein expression levels of ANG and EMT markers. The effects of ANG on proliferation, migration and invasion of squamous cell lung carcinoma cells was analyzed by Cell Counting Kit-8, scratch assay and Transwell invasion chamber in order to reveal the role of ANG in the process of EMT in squamous cell lung carcinoma. The results revealed that ANG was aberrantly expressed in the squamous cell lung carcinoma specimens and was closely correlated with the differentiation of the cell lines. The expression of ANG was also significantly associated with metastasis and the stage of the squamous cell lung carcinoma cases. In addition, we validated that ANG influenced the expression of vimentin, E-cadherin, N-cadherin, beta-catenin and TGF-beta1 in SK-MES-1 cells. Most importantly, overexpression of ANG enhanced the migration and invasion of SK-MES-1 cells, while knockdown resulted in opposite effects. In the present study, we found that ANG plays an important role in EMT in squamous cell lung carcinoma and may be a valuable therapeutic target for squamous cell lung carcinoma.