The current study investigated the molecular mechanisms underlying pediatric acute lymphoblastic leukemia (ALL) and screened for small molecular drugs as supplementary drugs to aid current therapy. Gene expression data of Gene Expression Omnibus (GEO) DataSet GSE42221, which consists of 7 primary human B-precursor samples and 4 control B-cell progenitor lymphoblast samples from patients with pediatric ALL, were downloaded from the public GEO database. Linear Models for Microarray Analysis package for R statistical software was used to identify differentially expressed genes (DEGs). Subsequently, biclustering analysis of DEGs was performed using pheatmap package for R. Functional enrichment analysis of DEGs was conducted using the Database for Annotation, Visualization and Integrated Discovery tool. Additionally, Search Tool for the Retrieval of Interacting Genes software was used to screen protein-protein interactions (PPIs) of the DEGs, and Connectivity Map database was employed to obtain small-molecule drugs that were significantly associated with DEGs. In total, 116 genes were identified as DEGs in pediatric ALL, including 56 downregulated and 60 upregulated genes. Functional enrichment analysis identified that upregulated DEGs, including marker of proliferation Ki-67, cyclin F and nucleolar and spindle associated protein 1, were significantly enriched in mesenchymal cell differentiation and development processes, whilst downregulated DEGs, including bone marrow morphogenetic protein 2, semaphoring 3F and ephrin B1 were enriched in cell cycle process. Amongst the DEGs, 169 PPIs were identified. Notably, carbimazole and quinostatin were associated with DEGs. Additionally, a number of DEGs were targeted by the two drugs, including signal transducer and activator of transcription 3, nucleolar and spindle associated protein 1 and cell division cycle 20. Mesenchymal cell differentiation and development as well as cell cycle processes may be important for pediatric ALL. Quinostatin may be used as a potent supplementary drug for treating pediatric ALL.

Cell-cycle-associated and expression-elevated protein in tumor (CREPT) functions as a cell cycle modulator that enhances the transcription of cyclin D1 by interacting with RNA polymerase II. CREPT has been identified to be overexpressed in various human cancer types; however, the expression and significance of CREPT in renal cell carcinoma (RCC) has remained largely elusive. In the present study, increased expression of CREPT was identified in 46.7% RCC tissues compared with adjacent normal tissue (31.1%; P=0.032) using immunohistochemistry. Furthermore, overexpression of CREPT was significantly associated with the Tumor-Node-Metastasis stage (χ2=11.967, P=0.001) and Fuhrman grade (χ2=15.453, P<0.001). In addition, increased expression of CREPT was associated with poor overall survival (P=0.021) and disease-free survival (P=0.015) of patients according to Kaplan-Meier analysis. Cellular function assays demonstrated that knockdown of CREPT in the 786-O and 769P RCC cell lines suppressed their proliferative, colony formation, migratory and invasive capacity and led to cell cycle arrest in the G1 phase. In addition, the western blotting analysis demonstrated that CREPT may control the cell cycle through downregulation of cyclin D1 and c-myc. Collectively, the overexpression of CREPT was indicated to be a negative prognostic factor for RCC, and CREPT may serve as a novel therapeutic target for the treatment of RCC.

An increased risk of renal cell carcinoma (RCC) has been linked with obesity and metabolic syndrome. However, the mechanisms by which lipid metabolic disorders affect the development of RCC remain unclear and highly controversial. Integrin-linked kinase (ILK) is a serine/threonine protein kinase involved in the regulation of tumor cell growth and angiogenesis. In the present study, the effect of free fatty acids in the promotion of RCC progression was investigated by upregulating ILK. Results of the MTT assay indicated that treatment of 786-O cells with oleic acid induced a concentration-dependent increase in cell viability. Flow cytometry analysis revealed that the effect of oleic acid on cell apoptosis was not significant. Following treatment with oleic acid, the expression of ILK, phospho-Akt and G protein-coupled receptor 40 (GPR40) was increased in 786-O cells. These effects were reversed when the expression of ILK was downregulated using specific small interfering RNA. These results indicate that free fatty acids are associated with the development of renal cell carcinoma via activation of the GPR40/ILK/Akt pathway, revealing a novel mechanism for the correlation between metabolic disturbance and renal carcinoma.