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.
Highlights
Liver cancer is one of the most common cancer type and the fifth leading cause of cancer-related death among men in the United States [1]
Compared to the normal group, the expression level of GTP-binding protein 4 (GTPBP4) mRNA was dramatically higher in hepatocellular carcinoma (HCC) tissues (P
Lee et al [8] revealed that down-regulation and infrequent mutation of GTPBP4 were observed in human glioma cell lines and primary tumors
Summary
Liver cancer is one of the most common cancer type and the fifth leading cause of cancer-related death among men in the United States [1]. The molecular characteristics of HCC have been explored broadly by the high-throughput sequencing methods [4, 5], biomarkers, which are crucial to HCC early diagnosis and effective targeted therapy, have remained rather unsatisfactory. To explore the molecular pathways and potential therapeutic target underlying HCC tumorigenesis and progression is still urgently needed. GTPBP4 mainly locates in the nucleolus [9], which is involved in the synthesis of 60S subunit [10] and maturation [11], closely related to cell proliferation and growth. The different expression levels of GTPBP4 (downregulated or upregulated) were found in those www.impactjournals.com/oncotarget malignant tumors, suggesting that GTPBP4 may act as an oncogene or a suppressor gene mainly dependent upon the specific cancer type. Whether GTPBP4 can be used as a potential therapeutic target for HCC needs to be investigated
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