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Regulation of long non-coding RNA (lncRNA) PVT1 on miR-125 affecting the metastasis of gastric cancer cells and the mechanism were investigated. qPCR was used to detect the expression of PVT1 and miR-125 in gastric cancer and paracancerous tissues, and the relationship between PVT1 and clinicopathological parameters of gastric cancer patients. Dual luciferase reporter gene was used to detect the mutual effect between PVT1 and miR-125. The clone formation assay was used to detect changes of proliferation behavior of gastric cancer cells after inhibition of PVT1. Transwell invasion assay was used to detect the changes of invasion ability of gastric cancer cells after inhibition of PVT1. Subcutaneous tumor formation in nude mice inhibited the effect of PVT1 on the tumor size and volume of gastric cancer cells. Compared with paracancerous tissues, the expression of PVT1 and miR-125 was significantly increased in gastric cancer tissues. There were no significant differences in the expression level of PVT1 between gastric cancer patients of different genders and ages. The higher the gastric cancer staging was, the more obvious the expression level of PVT1 in the tissues of patients with gastric cancer was, and the more obvious the expression of PVT1 in the tissues of patients with gastric lymph node metastasis was. PVT1 specifically bound to the 3′UTR of miR-125, whereas the inhibition of PVT1 inhibited the ability of proliferation and invasion of gastric cancer cells. In vitro experiment of tumor formation in nude mice showed that the tumor volume and weight of the tumor-bearing mice in the si-PVT1 group were significantly reduced. PVT1 plays an important role in the occurrence and development of gastric cancer, it can regulate the proliferation and invasion of gastric cancer cells by targeting miR-125 activity. [ABSTRACT FROM AUTHOR]

The high mortality rate of lung squamous cell carcinoma (LUSC) is in part due to the lack of early detection of its biomarkers. The identification of key molecules involved in LUSC is therefore required to improve clinical diagnosis and treatment outcomes. The present study used the microarray datasets GSE31552, GSE6044 and GSE12428 from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted to construct the protein-protein interaction network of DEGs and hub genes module using STRING and Cytoscape. The 67 DEGs identified consisted of 42 upregulated genes and 25 downregulated genes. The pathways predicted by KEGG and GO enrichment analyses of DEGs mainly included cell cycle, cell proliferation, glycolysis or gluconeogenesis, and tetrahydrofolate metabolic process. Further analysis of the University of California Santa Cruz and ONCOMINE databases identified 17 hub genes. Overall, the present study demonstrated hub genes that were closely associated with clinical tissue samples of LUSC, and identified TYMS, CCNB2 and RFC4 as potential novel biomarkers of LUSC. The findings of the present study contribute to an improved understanding of the molecular mechanisms of carcinogenesis and progression of LUSC, and assist with the identification of potential diagnostic and therapeutic targets of LUSC. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effect of bortezomib on heat shock protein 27 (HSP27) in multiple myeloma (MM) and provide a potential new target for clinical treatment. Peripheral blood was collected from 50 normal subjects and 50 patients with newly diagnosed MM and the expression of HSP27 was detected by ELISA. The changes of HSP27 after conventional vincristine, doxorubicin and dexamethasone (VAD) chemotherapy, and bortezomib plus VAD were compared. The effect of bortezomib on U266 cell proliferation and apoptosis was detected using a Cell Counting Kit-8 assay and Annexin V-FITC/propidium iodide double staining with flow cytometry. The content of HSP27 following bortezomib treatment was determined by ELISA. Western blot analysis and reverse transcription-quantitative PCR were used to detect the mRNA and protein expression of HSP27, Bax and Bcl-2. HSP27 expression was increased in patients with MM compared with healthy control subjects, and the expression was increased as the cancer progressed (P<0.05). Compared with the VAD chemotherapy group, the bortezomib plus VAD chemotherapy regimen significantly inhibited the expression of HSP27 (P<0.05), and the content of HSP27 was decreased in patients in which treatment was effective compared to those patients that exhibited disease progression (P<0.05). The efficacy of the treatment regimes was not associated with age or gender. Compared with the control group, bortezomib or OGX-427 (HSP27 inhibitor) treatment inhibited U266 cell proliferation, promoted U266 cell apoptosis (P<0.05) and significantly decreased HSP27 expression (P<0.05). Furthermore, the expression of HSP27 and Bcl-2 was significantly decreased, while the expression of Bax was increased by bortezomib and OGX-427 (P<0.05). There was no significant difference between the bortezomib and OGX-427 group in the in vitro analysis. HSP27 was positively correlated with Bcl-2 expression and negatively correlated with Bax expression in U266 cells. In conclusion, bortezomib promotes the apoptosis of MM cells, potentially by downregulating the expression of HSP27, providing a potential novel target for the clinical treatment of multiple myeloma. [ABSTRACT FROM AUTHOR]

The poor outcome of patients with esophageal squamous cell carcinoma (ESCC) highlights the importance of the identification of novel effective prognostic biomarkers. Long non-coding RNAs (lncRNAs) serve regulatory roles in various types of cancer. The aim of the present study was to investigate the lncRNA expression profile in ESCC and to identify lncRNAs associated with the prognosis of ESCC by performing comprehensive bioinformatics analyses. The RNA-sequencing (Seq) expression dataset GSE53625 generated from ESCC samples was used as a training dataset. Additional RNA-Seq datasets relative to ESCC samples were downloaded from The Cancer Genome Atlas and used as a validation dataset. Data were screened using the limma package, and differentially expressed lncRNAs between early- and late-stage ESCC were identified. A random forest algorithm was used to select the optimal lncRNA biomarkers, which were then analyzed using the support vector machine (SVM) algorithm with R software. The identified lncRNA biomarkers were examined in the validation dataset by bidirectional hierarchical clustering and using an SVM classifier. Subsequently, univariate and multivariate Cox regression analyses were performed to analyze the potential ability lncRNAs to predict the survival rate of patients with ESCC. By examining the training group, 259 deregulated lncRNAs between early- and advanced-stage ESCC were identified. Further bioinformatics analyses identified a nine-lncRNA signature, including AC098973, AL133493, RP11-51M24, RP11-317N8, RP11-834C11, RP11-69C17, LINC00471, LINC01193 and RP1-124C. This nine-lncRNA signature was used to predict the tumor stage and patient survival rate with high reliability and accuracy in the training and validation datasets. Furthermore, these nine lncRNA biomarkers were primarily involved in regulating the cell cycle and DNA replication, and these processes were previously identified to be associated with the progression of ESCC. The identified nine-lncRNA signature was identified to be associated with the tumor stage, and could be used as predictor of the survival rate of patients with ESCC. [ABSTRACT FROM AUTHOR]

Alsterpaullone (Alp) is a small-molecule inhibitor that targets cyclin-dependent kinases to inhibit tumor cell activity. However, to the best of our knowledge, the effect of Alp on hepatoblastoma has not been investigated. Therefore, the function of Alp in apoptotic induction of hepatoblastoma cells and a potential mechanism of action were investigated. Results indicated that low doses of Alp (1 µM) significantly induced apoptosis in the HepG2 hepatoblastoma cell line. In vivo experiments of tumor suppression further indicated that Alp (3 mg/kg) exerted an inhibitory effect on HepG2 ×enograft tumor growth. Following Alp treatment, the expression level of B-cell lymphoma 2 (Bcl-2)-associated X protein, and cleaved caspase-3 and −9 in HepG2 cells was significantly increased; however, the expression of Bcl-2 was significantly decreased. In addition, phosphorylation of p38 mitogen-activated protein kinase (MAPK) significantly decreased Alp-induced caspase-3 and −9 activation. These results suggested that Alp induces apoptosis and inhibited proliferation via the p38MAPK signaling pathway. Therefore, Alp may be a therapeutic agent for treating hepatoblastoma. [ABSTRACT FROM AUTHOR]

Human rotavirus (HRV) is the primary cause of severe gastroenteritis in children. However, there is currently no protective virus for rotavirus available. In the present study, an HRVVP7-cholera toxin B subunit (CTB) fusion protein was expressed in Arabidopsis thaliana. To determine the adjuvant effect of HRVVP7-CTB, HRVVP7 without CTB was expressed in the same manner. HRVVP7-CTB accounted for 0.39% of the total soluble protein (TSP) in the transgenic seeds and 52.65 µg/g of HRVVP7 protein was expressed in these seeds. Mice were immunized with TSP from the transformed seeds and produced serum immunoglobulin G (IgG) and mucosal IgA specifically directed against HRVVP7. Antibody titers were highest in mice orally immunized with the plant-expressed HRVVP7-CTB protein, whereas HRVVP7-CTB-specific IgG neutralized the rotavirus. Suckling pups born from dams immunized with the HRVVP7-CTB fusion protein were protected against challenge with virulent rotavirus. The results of the present study suggest that the HRVVP7-CTB fusion protein produced in A. thaliana may be a rotaviral-specific candidate subunit vaccine. [ABSTRACT FROM AUTHOR]

Germline mutations of DNA mismatch repair gene human MutS homolog 2 (hMSH2) are associated with hereditary nonpolyposis colorectal cancer (HNPCC). A total of one-third of these mutations are missense mutations. Several hMSH2 missense mutations have been identified in patients in East Asia, although their function has not been evaluated. In the present study, the role of ten hMSH2 missense mutations in the pathogenesis of colorectal cancer was examined. The hMSH2/hMSH6 protein interaction system was established using yeast two-hybrid screening. Next, the missense mutations were analyzed for their ability to affect the protein interaction of hMSH2 with its partner hMSH6. Additionally, the Sorting Intolerant from Tolerant tool was applied to predict the effects of different amino acid substitutions. The results demonstrated that certain hMSH2 mutations (L173R and C199R) caused a significant functional change in the human hMutSα complex and were identified to be pathological mutations. The Y408C, D603Y, P696L and S703Y mutations partially affected interaction and partly affected the function of hMSH2. The remaining four variants, T8M, I169V, A370T and Q419K, may be non-functional polymorphisms or could affect protein function through other molecular mechanisms. The present study evaluated the functional consequences of previously unknown missense mutations in hMSH2, and may contribute to improved clinical diagnosis and mutation screening of HNPCC. [ABSTRACT FROM AUTHOR]

Breast cancer is the worldwide leading cause of cancer-related deaths among women. Increasing evidence has demonstrated that microRNAs (miRNAs) play critical roles in the carcinogenesis and progression of breast cancer. miR-653-5p was previously reported to be involved in cell proliferation and apoptosis. However, the role of miR-653-5p in the progression of breast cancer has not been studied. In the present study, it was found that overexpression of miR-653-5p significantly inhibited the proliferation, migration and invasion of breast cancer cells in vitro. Moreover, overexpression of miR-653-5p promoted cell apoptosis in breast cancer by regulating the Bcl-2/Bax axis and caspase-9 activation. Additionally, the epithelial-mesenchymal transition and activation of the Akt/mammalian target of rapamycin signaling pathway were also inhibited by miR-653-5p. Furthermore, the data demonstrated that miR-653-5p directly targeted mitogen-activated protein kinase 6 (MAPK6) and negatively regulated its expression in breast cancer cells. Upregulation of MAPK6 could overcome the inhibitory effects of miR-653-5p on cell proliferation and migration in breast cancer. In conclusion, this study suggested that miR-653-5p functions as a tumor suppressor by targeting MAPK6 in the progression of breast cancer, and it may be a potential target for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancer types with a poor prognosis due to the lack of symptoms in the early stages and a delayed diagnosis. The present study aimed to identify the risk factors significantly associated with prognosis and to search for novel effective diagnostic modalities for patients with early-stage ESCC. mRNA and methylation data of patients with ESCC and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database, and the representation features were screened using deep learning autoencoder. The univariate Cox regression model was used to select the prognosis-related features from the representation features. K-means clustering was used to cluster the TCGA samples. Support vector machine classifier was constructed based on the top 75 features mostly associated with the risk subgroups obtained from K-means clustering. Two ArrayExpress datasets were used to verify the reliability of the obtained risk subgroups. The differentially expressed genes and methylation genes (DEGs and DMGs) between the risk subgroups were analyzed, and pathway enrichment analysis was performed. A total of 500 representation features were produced. Using K-means clustering, the TCGA samples were clustered into two risk subgroups with significantly different overall survival rates. Joint multimodal representation strategy, which showed a good model fitness (C-index=0.760), outperformed early-fusion autoencoder strategy. The joint representation learning-based classification model had good robustness. A total of 1,107 DEGs and 199 DMGs were screened out between the two risk subgroups. The DEGs were involved in 70 pathways, the majority of which were correlated with metastasis and proliferation of various cancer types, including cytokine-cytokine receptor interaction, cell adhesion molecules PPAR signaling pathway, pathways in cancer, transcriptional misregulation in cancer and ECM-receptor interaction pathways. The two survival subgroups obtained via the joint representation learning-based model had good robustness, and had prognostic significance for patients with ESCC. [ABSTRACT FROM AUTHOR]