The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma.
Yan-yang Gao,Zhuo-yan Ling,Yun-Rong Zhu,Ce Shi,Yin Wang,Xiang-yang Zhang,Zhi-qing Zhang,Qin Jiang,Min-Bin Chen,Shuo-fei Yang,Cong Cao,Cong Cao +11 more
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TLDR
In this article, genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells.Abstract:
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.read more
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The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo
Jin Yao,Xinjing Wu,Qing Yu,Shuo-fei Yang,Jin Yuan,Zhi-qing Zhang,Jinsong Xue,Qin Jiang,Min-Bin Chen,Guan-Hua Xue,Cong Cao +10 more
TL;DR: Together, PCK1 is essential for angiogenesis possibly by mediating Gαi3 expression and Akt activation possibly bymediating G αi3expression and AkT activation.
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Identification of Gαi3 as a promising target for osteosarcoma treatment
Zhengyue Bian,Hua-jian Shan,Yunrong Zhu,Ce Shi,Min-Bin Chen,Yumin Huang,Xiaodong Wang,Xiaozhong Zhou,Cong Cao +8 more
TL;DR: In vivo studies showed that Gαi3 shRNA AAV intratumoral injection largely inhibited the growth of subcutaneous xenografts of primary OS cells, and growth of the G αi3-knockout primary OS xenogsrafts was much slower than that of OS xenografteds with empty vector.
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HBO1 overexpression is important for hepatocellular carcinoma cell growth.
TL;DR: In this article, the authors show that HBO1 mRNA and protein expression is elevated in human hepatocellular carcinoma (HCC) tissues and HCC cells and that ectopic overexpression of HBO1 by a lentiviral construct augmented HCC cell proliferation, migration and invasion.
Journal ArticleDOI
HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth
Tengfei Chen,Huiting Hao,Yan Zhang,Xiao-Yu Chen,Huaqing Zhao,Rui Yang,Ping Li,Ling-xiao,Qiu,Yong-hua Sang,Chunbo Xu,Shaochuan Liu +11 more
TL;DR: In primary and immortalized NSCLC cells, HBO1 shRNA robustly inhibited cell viability, proliferation and migration and HBO1 knockout by CRISPR/Cas9 induced significant anti-tumor activity in NSCLc cells.
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The role of protein acetylation in carcinogenesis and targeted drug discovery
TL;DR: The roles ofprotein acetylation in tumor pathology and therapeutic drugs targeting protein acetylations are discussed, which offers the contributions of protein acetolation in clarification of carcinogenesis, and discovery of therapeutic drugs for cancers, and lays the foundation for precision medicine in oncology.
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