Abstract
Hepatocellular carcinoma (HCC) is a common primary liver malignancy lacking effective molecularly-targeted therapies. HBO1 (lysine acetyltransferase 7/KAT7) is a member of MYST histone acetyltransferase family. Its expression and potential function in HCC are studied. We show that HBO1 mRNA and protein expression is elevated in human HCC tissues and HCC cells. HBO1 expression is however low in cancer-surrounding normal liver tissues and hepatocytes. In HepG2 and primary human HCC cells, shRNA-induced HBO1 silencing or CRISPR/Cas9-induced HBO1 knockout potently inhibited cell viability, proliferation, migration, and invasion, while provoking mitochondrial depolarization and apoptosis induction. Conversely, ectopic overexpression of HBO1 by a lentiviral construct augmented HCC cell proliferation, migration and invasion. In vivo, xenografts-bearing HBO1-KO HCC cells grew significantly slower than xenografts with control HCC cells in severe combined immunodeficient mice. These results suggest HBO1 overexpression is important for HCC cell progression.
Highlights
Liver cancer is the fifth most common cancer and the2th leading cause of cancer-related human mortalities globally, with over 840,000 new cases and 780,000 deaths reported each year[1,2]
HBO1 is upregulated in human hepatocellular carcinoma (HCC) tissues and cells First, we tested the expression of HBO1 in human HCC
Through searching the UALCAN database, we found that HBO1 mRNA expression in liver cancer tissue specimens is significantly higher than that in normal liver tissues (P < 0.01, Fig. 1A)
Summary
Liver cancer is the fifth most common cancer and the. 2th leading cause of cancer-related human mortalities globally, with over 840,000 new cases and 780,000 deaths reported each year[1,2]. Of which 75–80% of liver cancer is hepatocellular carcinoma (HCC), the latter is considered as a major health threat globally[3,4]. The overall five-year survival of HCC is far more from satisfactory[5]. The current treatments for HCC are limited, and sorafenib is the only molecularly targeted agent[3,4]. HCC’s incidence has been steadily rising, especially in Western countries[3,4]. It is extremely urgent to explore and develop novel antiHCC strategies and molecularly-targeted agents[6,7]
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