HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. Methods: HBO1 expression was tested in human OS tissues and cells. Genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells. The HBO1 inhibitor WM-3835 was utilized to block HBO1 activation. Results: HBO1 mRNA and protein expression is significantly elevated in OS tissues and cells. In established (MG63/U2OS lines) and primary human OS cells, shRNA-mediated HBO1 silencing and CRISPR/Cas9-induced HBO1 knockout were able to potently inhibit cell viability, growth, proliferation, as well as cell migration and invasion. Significant increase of apoptosis was detected in HBO1-silenced/knockout OS cells. Conversely, ectopic HBO1 overexpression promoted OS cell proliferation and migration. We identified ZNF384 (zinc finger protein 384) as a potential transcription factor of HBO1. Increased binding between ZNF384 and HBO1 promoter was detected in OS cell and tissues, whereas ZNF384 silencing via shRNA downregulated HBO1 and produced significant anti-OS cell activity. In vivo , intratumoral injection of HBO1 shRNA lentivirus silenced HBO1 and inhibited OS xenograft growth in mice. Furthermore, growth of HBO1-knockout OS xenografts was significantly slower than the control xenografts. WM-3835, a novel and high-specific small molecule HBO1 inhibitor, was able to potently suppressed OS cell proliferation and migration, and led to apoptosis activation. Furthermore, intraperitoneal injection of a single dose of WM-3835 potently inhibited OS xenograft growth in SCID mice. Conclusion: HBO1 overexpression promotes OS cell growth in vitro and in vivo.
In China's rapid economic growth and significant increase in the process of urbanization, a large number of foreign direct investment may play an impeccable role. We establish a Vector Auto-Regressive (VAR) model and make empirical research by using foreign direct investment, the urbanization and economic growth of quarterly data in China from 1999 to 2015. Then we use the unit root test, cointegration test, error correction model and Granger causality test to analyze three factors, and use impulse response function diagrams to analyze the relationship among FDI, urbanization and economic growth. The empirical results show that there is a cointegration relationship among FDI, urbanization and GDP. FDI and economic growth are granger causality each other, urbanization is the granger cause of FDI. Meanwhile, economic growth is the granger cause of urbanization. In the long run, improve domestic infrastructure construction and absorb foreign capital into domestic capital market are helpful to drive China's economic growth. The influence of urbanization on foreign investment continues to rise, meaning that urban development has pull effect to foreign investment. The departments concerned should encourage entrance of foreign capital to provide appropriate for the convenience of various kinds of production factors. At the same time, government should improve national awareness to stimulate consumption of foreign capital. What is more, we should accelerate the speed of urbanization, increase the intensity of financial expenditure to urbanization and increase the domestic economy by introducing foreign capital and city development.
<p class="1"><span lang="EN-US">With the rapid development of the financial system in recent years, all kinds of financial derivatives teem and the size of the shadow banking is becoming more and bigger. It has become an important factor affecting the stability of China’s financial system. The influence of shadow banks on the financial system has two sides, on the one hand it is advantageous to the development and expansion of small and medium-sized enterprises as lubricant of corporate financing, on the other hand, features of shadow banking that highly leveraged and term mismatch also bring uncertainty to China’s financial system. Firstly, this paper calculates the size of the shadow banking in China, and then builds a fuzzy comprehensive evaluation system to evaluate the risk of China’s financial system. When determining the evaluation index, this paper apply KMV model to calculate the credit risk of China’s securities market, and the maximum entropy method to determine the index weight. After getting China’s financial system risk index and the size of shadow banking, this paper constructs the VAR model and makes the parameter estimation and impulse response analysis. Analysis results show that in a certain degree, the increase of the scale of shadow banks can reduce the risk of the financial system, but if it is over some certain threshold, it will increase the overall risk of the financial system.</span></p>
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