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Introduction
Gastric cancer is a kind of tumor with high morbidity and mortality [1]. Although surgical treatment, chemotherapy and radiotherapy could greatly improve the survival of patients with gastric cancer, which could not be cured or recurred within several years [2]. Thus, it is very important for patients with gastric cancer to get early diagnosis and treatment, and it is an urgent need to find new targets for treating or predicting gastric cancer.
P53 has been proved to play important roles in gastric cancer progression. For example, p53 deregulation is closely associated with Epstein-Barr virus-associated gastric cancer [3]. P53 loss could drive gastric tumorigenesis [4]. On the contrary, activating p53/caspase-3 signaling could suppress gastric cancer progression [5]. Based on the critical roles of p53 in tumor progression, researchers had been investigating the mechanisms regulating p53 expression. NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner [6]. During mitotic catastrophe, chromosomal breaks could trigger gammaH2AX-ATM-p53-mediated apoptosis [7]. However, the detailed mechanisms regulating p53 expression in gastric cancer are not well-defined.
Previous study investigated the protein interaction profiles of Drosophila p53 and uncovered additional nodes of human p53 network via a genome-scale assay [8], in which GTPBP4 (guanosine triphosphate binding protein 4), also known as Nog1, was identified as an interactor and GTPBP4 knockdown induced p53 activation in the absence of nucleolar disruption. Previous study has shown that TOR regulates late steps of ribosome maturation in the nucleoplasm via GTPBP4 in response to nutrients, and GTPBP4 is required for biogenesis of the 60 S ribosomal subunit [9, 10]. Importantly, in wide-type p53 breast tumors, GTPBP4 expression is negatively correlated with patient survival, demonstrating a potential relevance of GTPBP4-p53 interaction in cancers. Recently, Yu, H et al. indicated that upregulation of GTPBP4 is responsible for colorectal tumor metastasis [11]. However, the roles of GTPBP4 and GTPBP4-p53 interaction have not been revealed in gastric cancer progression.
Here, GTPBP4 expression was meaured in gastric cancer and normal adjacent tissues, and we found that GTPBP4 expression was significantly increased in gastric cancer tissues and positively correlated with gastric cancer stages. Further GTPBP4-stable knockdown gastric cancer cells were constructed, and used to evaluate the effects of GTPBP4 in cell proliferation and apoptosis. Additionally, RNA-based high-throughput sequencing...