The present study aimed to determine the differential expression profiles of proteins in endometrial carcinoma and to screen the proteins associated with the occurrence and development of endometrial cancer (EC). In total, 15 samples of human EC and paracancerous tissues were selected for proteomic analysis using a label-free quantification method based on liquid chromatography-tandem mass spectrometry. The differential proteins were analysed using bioinformatics and verified using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Finally, the expression of differential proteins in 75 endometrial carcinoma samples and 30 normal endometrial tissue samples were detected using immunohistochemical staining, and the associations between differential protein expression and clinicopathological features were analysed. In total, 579 up-regulated proteins and 346 down-regulated proteins were identified between the two groups and seven proteins with the most significant differences were selected; these proteins included interferon-induced protein with tetratricopeptide repeats 3, poly(ADP-ribose) polymerase family member 9, solute carrier family 34 member 2, cytochrome b5 reductase 1, protein tyrosine phosphatase non-receptor type 1, dermatopontin (DPT) and secretory leukocyte peptidase inhibitor. RT-qPCR and western blotting showed that DPT expression was down-regulated (P<0.001), which was consistent with the mass spectrometry results. The immunohistochemical staining results showed that the positive expression of DPT in EC and normal endometrial tissues was statistically significant (P<0.001). The positive expression of DPT was significantly decreased in poorly differentiated, late stage, lymph node metastasis and myometrial invasion depth ≥1/2 samples (P<0.05). DPT expression was significantly lower in EC, which might play role in the pathogenesis of EC.

Erastin is a small molecular compound that induces ferroptosis by binding to voltage-dependent anion-selective channel protein (VDAC)2, VDAC3 and solute carrier family 7 member 5 inhibiting the cystine/glutamate antiporter. However, to the best of our knowledge, the mechanism of erastin-induced breast cancer cell death remains unclear. In present study aimed to explore the underlying mechanisms of the antitumor effects of erastin on breast cancer cells. Cellular viability was assessed using an MTT assay, a lactate dehydrogenase cytotoxicity assay kit was used to determine the cell death rate, the intracellular Fe2+ levels were determined using an iron colorimetric assay kit and western blotting was used to estimate the changes of autophagy-associated proteins levels. The present study demonstrated that erastin inhibited the viability of breast cancer cells and induced breast cancer cell death in a dose-dependent manner. Additionally, autophagy was activated by erastin, as demonstrated by upregulated expression levels of autophagy-associated proteins in breast cancer cells. Bafilomycin A1, 3-methyladenine and knockdown of autophagy related (ATG)5 with small interfering RNA prevented erastin-induced breast cancer cell death and inhibited the erastin-induced changes in the expression levels of the autophagy-associated proteins beclin1, ATG5, ATG12, microtubule-associated proteins 1A/1B light chain 3B (LC3B) and P62. Furthermore, erastin-induced breast cancer cell death was inhibited by an iron chelator, deferoxamine, which inhibited the increases of erastin-induced iron levels and inhibited the erastin-induced changes in the expression levels of the autophagy-related proteins beclin1, ATG5, ATG12, LC3B and P62. In summary, erastin triggered autophagic death in breast cancer cells by increasing intracellular iron levels.

The present study aimed to reveal the key long non-coding RNAs (lncRNAs) and the potential molecular mechanisms of XAV939 treatment in non-small cell lung cancer (NSCLC). The NSCLC cell line, NCI-H1299, was cultured with 10 µM XAV939 for 12 h, and NCI-H1299 cells without XAV939 treatment were used as controls. Following RNA isolation from the two groups, RNA-sequencing was performed to detect transcript expression levels, and differentially-expressed lncRNAs (DE-lncRNAs) and DE-genes (DEGs) were identified between groups and analyzed for their functions and associated pathways. The potential associations between proteins encoded by DEGs were revealed via a protein-protein interaction (PPI) network. Subsequently, the microRNA (miRNA/miR)-mRNA, lncRNA-miRNA and lncRNA-mRNA interactions were explored, followed by competing endogenous RNA (ceRNA) network construction. A total of 396 DEGs and 224 DE-lncRNAs were identified between the XAV939 and control groups. These lncRNAs were mainly enriched in pathways such as 'ferroptosis' [DEG, solute carrier family 7 member 11 (SLC7A11)]. The PPI network consisted of 97 nodes and 112 interactions. Furthermore, a total of 10 noteworthy lncRNAs were revealed in the DE-lncRNA-DEG interaction. Finally, the lncRNA-miRNA-mRNA regulatory association, including MIR503 host gene (MIR503HG)-miR1273c-SRY-box 4 (SOX4), was explored in the current ceRNA network. The downregulation of lncRNA MIR503HG induced by XAV939 may serve an important role in NSCLC suppression via sponging miR-1273c and regulating SOX4 expression. Furthermore, the downregulation of SLC7A11 induced by XAV939 may also inhibit the development of NSCLC via the ferroptosis pathway.

The aim of the present study was to identify the biomarkers involved in the development of hepatocellular adenoma (HCA) through integrated analysis of gene expression and methylation microarray. The microarray dataset GSE7473, containing HNF1α-mutated HCA and their corresponding non-tumor livers, 5 HNF1α-mutated HCA and 4 non-related non-tumor livers, was downloaded from the Gene Expression Omnibus (GEO) database. The DNA methylation profile GSE43091, consisting of 50 HCA and 4 normal liver tissues, was also downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by the limma package of R. A t-test was conducted on the differentially methylated sites. Functional enrichment analysis of DEGs was performed through the Database for Annotation, Visualization and Integrated Analysis. The genes corresponding to the differentially methylated sites were obtained by the annotation files of methylation chip platform. A total of 182 DEGs and 3,902 differentially methylated sites were identified in HCA. In addition, 238 enriched GO terms, including organic acid metabolic process and carboxylic acid metabolic process, and 14 KEGG pathways, including chemical carcinogenesis, were identified. Furthermore, 12 DEGs were identified to contain differentially methylated sites, among which, 8 overlapped genes, including pregnancy zone protein and solute carrier family 22 member 1 (SLC22A1), exhibited inverse associations between gene expression levels and DNA methylation levels. The DNA methylation levels may be potential targets of HCA. The present study revealed that the 8 overlapped genes, including annexin A2, chitinase 3-like 1, fibroblast growth factor receptor 4, mal, T-cell differentiation protein like, palladin, cytoskeletal associated protein, plasmalemma vesicle associated protein and SLC22A1, may be potential therapeutic targets of HCA.

Lung squamous cell carcinoma (LSCC) exhibits a number of similarities with lung adenocarcinoma (LA) in terms of copy number alterations. However, compared with LA, the range of genetic alterations in LSCC is less understood. In the present study, a large-scale literature-based search of LA-associated genes and LSCC-associated genes was performed to identify the genetic basis in common with these two diseases. For each of the LA-associated genes, a mega-analysis was performed to test its expression variations in LSCC using 11 RNA expression datasets, with significant genes identified using statistical analysis. Subsequently, a functional pathway analysis was performed to identify a possible association between any of the significant genes identified from the mega-analysis and LSCC, followed by a co-expression analysis. A multiple linear regression (MLR) model was employed to investigate the possible influence of sample size, country of origin and study date on gene expression in patients with LSCC. Disease-gene association data analysis identified 1,178 genes involved in LA, 334 in LSCC, with a significant overlap of 187 genes (P<1.02×-161). Mega-analysis revealed that three LA-associated genes, such as solute carrier family 2 member 1 (SLC2A1), endothelial PAS domain protein 1 (EPAS1) and cyclin-dependent kinase 4 (CDK4), were significantly associated with LSCC (P<1.60×10-8), with multiple potential pathways identified by functional pathway analysis, which were further validated by co-expression analysis. The present MLR analysis suggested that the country of origin was a significant factor for the levels of expression of all three genes in patients with LSCC (P<4.0×10-3). Collectively, the present results suggested that genes associated with LA should be further investigated for their association with LSCC. In addition, SLC2A1, EPAS1 and CDK4 may be novel risk genes associated with LA and LSCC.