Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular carcinoma and its prognostic significance

Abstract

GTP-binding protein 4 (GTPBP4), as a novel member of GTPases involved in the synthesis of 60S subunit and maturation, is closely related to cell proliferation and growth. Till now, a small number of existing studies have found a contradictory dual role of GTPBP4 in cancer. Whether the expression level of GTPBP4 in hepatocellular carcinoma (HCC) is associated with the patients' prognosis or its function and underlying molecular mechanisms still remains unclear. In the present study, the above issues were explored for the first time. Our results showed that GTPBP4 was overexpressed in HCC and knockdown of GTPBP4 delayed cell proliferation, impaired colony formation ability, induced cell cycle arrest in G2/M period and promoted apoptosis in HCC cell lines. Besides, in vivo xenograft nude mice model revealed that GTPBP4 knockdown could significantly suppress HCC tumorigenesis. Gene microarray and further pathway enrichment analyses indicated that ERBB signaling pathway was the most significantly changed one. More importantly, high GTPBP4 expression level significantly correlated to the poor prognosis of HCC patients. Taken together, all these findings suggest that GTPBP4 serves as an oncogene and plays a pivotal role in HCC development, which will be a potential therapeutic target or a biomarker for HCC.