GTPBP4 Promotes Gastric Cancer Progression via Regulating P53 Activity

Abstract

Background/Aims: gastric cancer is a serious health concern with high morbidity and mortality. Therefore, it is urgent to find novel targets for gastric cancer diagnosis and treatment. Methods: qRT-PCR and immunohistochemistry assays were used to detect GTPBP4 expression in gastric cancer tissues, and gastric cancer and gastric epithelial cells. Lentivirus infection was used to construct GTPBP4 stable knockdown cells. Annexin V/PI apoptosis, CCK8, EdU incorporation and cell clone formation analysis were performed to evaluate the effects of GTPBP4 on gastric cancer cell proliferation and apoptosis. Further RNA-based high-throughput sequencing and co-IP assays were constructed to explore the related mechanisms contributing to GTPBP4-mediated effects. Results: GTPBP4 expression was significantly increased in gastric cancer tissues compared with that in adjacent normal tissues, and positively correlated with gastric cancer stages. Meanwhile, GTPBP4 level was markedly upregulated in gastric cancer cells than in gastric epithelial cells. Additionaly, stable knockdown of GTPBP4 inhibited cell proliferation and promoted cell apoptosis. Mechanistically, p53 and its related signaling were significantly activated in GTPBP4 stable knockdown cells. And GTPBP4 interacted with p53 in gastric cancer cells. Conclusions: our results provide insights into mechanistic regulation and linkage of the GTPBP4-p53 in gastric cancer, and also a valuable potential target for gastric cancer.

Determining the Clinical Value and Critical Pathway of GTPBP4 in Lung Adenocarcinoma Using a Bioinformatics Strategy: A Study Based on Datasets from The Cancer Genome Atlas

“…However, recent studies have indicated that the role of GTPBP4 in malignant tumor types is double sided. Although GTPBP4 has been most often found to act as an oncogene [ 12 , 13 ], it has also been described as a suppressor gene in rare cases, such as in neurofibromatosis 2 (NF2) [ 9 ], suggesting that the role of GTPBP4 depends on the specific type of cancer.…”

“…For example, aberrantly expressed GTPBP4 was found to be significantly associated with low survival probability in patients with HCC and breast cancer [ 15 , 21 ]. Yu et al concluded that GTPBP4 was responsible for tumor metastasis in CRC [ 14 ], and Li et al suggested that GTPBP4 promotes gastric cancer progression [ 12 ]. The analysis of its potential target genes in the present study suggested that GTPBP4 may be a predictor of survival in LUAD cases.…”

“…Therefore, we speculated that the regulation of ribosome biogenesis by GTPBP4 plays an essential role in various types of cancer. Regarding promoted progression of gastric cancer by GTPBP4 regulation of P53 activity [ 12 ], we infer that aberrant GTPBP4 affects LUAD cell proliferation, apoptosis, and migration by disturbing the balance between ribosome biogenesis and P53 activity. Thus, GTPBP4 is likely to participate in LUAD by regulating ribosomal biogenesis.…”

“…Guanosine triphosphate-binding protein 4 (GTPBP4), also known as CRFG [ 8 ], NGB [ 9 ], and NOG1 [ 10 ], is a GTPase involved in the synthesis of 60S ribosomal subunit and located on nuclear chromosome 10p15-14 [ 11 ]. Previous studies had shown that GTPBP4 can induce cell proliferation and enhance cell colony formation in some cancer types [ 12 , 13 ]. A study of colorectal carcinoma (CRC) also uncovered that GTPBP4 was responsible for tumor metastasis [ 14 ].…”

A clinical metabolomics‑based biomarker signature as an approach for early diagnosis of gastric cardia adenocarcinoma

“…Systems biology and high-throughput screening methods have revealed that the incidence of GCA is associated with mutations in tumor protein P53 (18,19) and the vitamin D receptor (20), as well as polymorphisms in the Fas ligand gene (21) and thymidylate synthase (22). In addition, proteins such as cancer antigen 125 and minichromosome maintenance 5 serve as potential biomarkers for the early diagnosis of GCA (23,24).…”