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. 2021 May 5;12(13):3819-3826.
doi: 10.7150/jca.48340. eCollection 2021.

GTPBP2 positively regulates the invasion, migration and proliferation of non-small cell lung cancer

Liu Jie  1   2 , Li Cong  1   3 , Wei Conghui  1 , Gao Ying  1
Affiliations

GTPBP2 positively regulates the invasion, migration and proliferation of non-small cell lung cancer

Liu Jie et al. J Cancer. .

Abstract

Lung cancer is one of the most common malignant tumors in the world, and the mortality rate ranks first among various malignant tumors. GTP-binding proteins (guanosine 5'-triphosphate-binding proteins, GTPBPs) are a type of protein with signal transduction function, have GTP hydrolase activity, and play an important role in cell signal transmission, cytoskeletal regulation, protein synthesis and other activities. GTPBP2 is one of the members of the G protein superfamily. Research on GTPBP2 is currently focused on human genetics, and its research in tumors has not been reported. First, Western blot and quantitative real-time PCR were used to analyze the expression differences of 12 cases of GTPBP2 in human NSCLC fresh cancer tissues and adjacent tissues. Then we selected 112 cases of NSCLC cancer tissues and 65 adjacent tissues for immunohistochemistry experiments to analyze the relationships between the expression of GTPBP2 and clinical pathological parameters and prognosis, we found that GTPBP2 is highly expressed in NSCLC cancer tissues, and the high expression of GTPBP2 is related to pTNM stage and lymph node metastasis. In addition, after GTPBP2 knockdown, GTPBP2 can promote the proliferation and invasion of NSCLC cell lines by up-regulating RhoC and MMP-9, and up-regulate cyclinD1, CDK4 and c-myc, and down-regulate P27 to promote the invasion of NSCLC cell lines. In addition, GTPBP2 negatively regulates Axin to promote β-catenin expression, thereby activating Wnt/β-catenin signaling, and promoting the occurrence of NSCLC.

Keywords: GTPBP2; cell invasion; cell migration; cell proliferation; non-small cell lung cancer..

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Expression pattern of GTPBP2. A, GTPBP2 expression in non-small lung cancer (NSCLC) cell lines with a normal bronchial cell line (16HBE). B and C, GTPBP2 expression in non-small lung cancer (NSCLC) cancer tissues and normal tissues, analyzed by immunocytochemistry, and assessed by ImageJ software. D, GTPBP2 expression in non-small lung cancer (NSCLC) cancer tissues and normal tissues, analyzed by quantitative real-time PCR expression (P<0.05).
Figure 2
Figure 2
A, GTPBP2 protein expression analyzed by immunocytochemistry in (a) squamous cell carcinoma and (b)adenocarcinoma, with (c)normal bronchial and (d)alveolar epithelial cells. Magnificatin,X200. B, Survival of NSCLC patients with high and low GTPBP2 expression analyzed based on Kaplan-Meier Curves (P<0.05).
Figure 3
Figure 3
Effect of GTPBP2 expression on the migration and invasion of non-small cell lung cancer (NSCLC) cells. A549 was transfected with specific shRNA-GTPBP2 and shRNA-NC. A and B, the cell migration analyzed by scratch test, and analyzed by Graphpad prism5(shRNA-GTPBP2 vs shRNA-NC, P<0.05). C and D, the cell invasion analyzed by transwell test, and analyzed by ImageJ-32(shRNA-GTPBP2 vs shRNA-NC, P<0.05). E, Expression of GTPBP2 in cell migration and invasion related proteins in A549 cell. F, Cell proliferation analyzed by CCK8, and analyzed by Graphpad prism5(shRNA-GTPBP2 vs shRNA-NC, P<0.05). G and H, the effect of GTPBP2 expression on cell proliferation and Wnt/β-catenin signaling pathway related proteins. (shRNA-GTPBP2 vs shRNA-NC, P<0.05).
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