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Lung cancer is the leading cause of cancer-related death worldwide, and the most common histologic subtype is lung adenocarcinoma (LUAD). Due to the significant mortality and morbidity rates among patients with LUAD, the identification of novel biomarkers to guide diagnosis, prognosis, and therapy is urgent. Guanosine triphosphate-binding protein 4 (GTPBP4) has been found to be associated with tumorigenesis in recent years, but the underlying molecular mechanism remains to be elucidated. In the present study, we demonstrate that GTPBP4 is significantly overexpressed in LUAD primary tumors. A total of 55 genes were identified as potential targets of GTPBP4. GO enrichment analysis identified the top 25 pathways among these target genes, among which, ribosome biogenesis was shown to be the most central. Each target gene demonstrated strong and complex interactions with other genes. Of the potential target genes, 12 abnormally expressed candidates were associated with survival probability and correlated with GTPBP4 expression. These findings suggest that GTPBP4 is associated with LUAD progression. Finally, we highlight the importance of the role of GTPBP4 in LUAD in vitro. GTPBP4 knockdown in LUAD cells inhibited proliferation and metastasis, promoted apoptosis, and enhanced sensitivity to TP. Overall, we conclude that GTPBP4 may be considered as a potential biomarker of LUAD. [ABSTRACT FROM AUTHOR]

The treatment of renal cell carcinoma (RCC) with chemotherapy remains a challenge; therefore, improving the knowledge of the molecular mechanisms underlying RCC chemoresistance and developing novel therapeutic strategies is important. Dedicator of cytokinesis 1 (DOCK1), the first member of the DOCK family to be discovered, displays various roles during tumorigenesis; however, its role during RCC progression is not completely understood. Therefore, the present study aimed to clarify the function of DOCK1 and 1-[2-(3′-(trifluoromethyl)-(1,1′-biphenyl)-4-yl)-2-oxoethyl]-5-pyrrolidinylsulfonyl-2 (1H)-pyridone (TBOPP), a DOCK1-sensitive inhibitor, during RCC development and chemoresistance. The results of CCK-8 and EdU assay indicated that TBOPP decreased RCC cell viability and proliferation compared with the control group, and sensitized RCC cells to cisplatin. Moreover, RCC cells with high DOCK1 expression levels displayed increased resistance to cisplatin, whereas DOCK1 knockdown enhanced the lethal effects of cisplatin on RCC cells. Furthermore, the results determined by western blotting, CCK-8 and cell apoptosis assay indicated that TBOPP effectively reduced DOCK1 expression levels compared with the control group, and the TBOPP-mediated cisplatin sensitizing effect was mediated by DOCK1 inhibition. The present study suggests that DOCK1 plays a vital role in RCC cell chemoresistance to cisplatin; therefore, TBOPP may serve as a novel therapeutic agent for RCC chemoresistance. [ABSTRACT FROM AUTHOR]