The clinical significance and potential molecular mechanism of integrin subunit beta 4 in laryngeal squamous cell carcinoma

The relationship between integrin beta 4 (ITGB4) expression and laryngeal squamous cell carcinoma (LSCC) remains unclarified. The object of the present study was to explore the clinical significance and potential molecular mechanism of ITGB4 in LSCC. The protein level of ITGB4 was significantly higher in 46 LSCC patients than in 26 non-LSCC tissues detected by in-house immunohistochemistry. Consistently, ITGB4 mRNA level was also greatly upregulated based on microarray and RNA-seq data (standard mean difference, SMD = 1.62, 95 % CI: 1.23–2.00). And the area under curves (AUC) of summary receiver operator characteristic (SROC) was 0.87 (95 % CI: 0.84–0.90) based on 172 cases of LSCC and 59 cases of non-cancerous controls. Ninety genes were intersected by the ITGB4 related genes and LSCC differential expressed genes (DEGs) from all available microarray and RNA-seq datasets. Based on Gene Ontology (GO) analysis, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) for the 90 ITGB4 related DEGs were extracellular matrix organization, basement membrane and extracellular matrix structural constituent, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that ITGB4 related DEGs mainly participated in the pathways of ECM-receptor interaction, Focal adhesion and Small cell lung cancer. Moreover, the Protein-Protein Interaction (PPI) network indicated that ITGA3, ITGA5, ITGB4, MET, LAMA3, and COL4A1 might be the core genes of LSCC development related to ITGB4. In conclusion, high ITGB4 expression may lead to the occurrence and development of LSCC via various signaling pathways.     

Heterogenous Populations of Tissue-Resident CD8+ T Cells Are Generated in Response to Infection and Malignancy

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The expression profile of circRNA and its potential regulatory targets in the placentas of severe pre-eclampsia

ObjectiveTo determine the expression profiles of circular RNAs (circRNAs) of women with severe pre-eclampsia (sPE group) versus normal pregnancies (normal control group).Materials and methodsRNA-sequencing (RNA-seq) was conducted to characterize differentially expressed circRNAs and mRNAs in the placental tissues of women with sPE versus normal pregnancies. circRNA functions were predicted by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis. The backsplicing junctions of circRNAs were validated with the use of divergent primers. Relative expression levels of cirRNAs were verified by quantitative real-time PCR (qPCR). A circRNA-miRNA-mRNA interaction network was constructed to outline the regulatory network of the differentially expressed circRNAs.ResultsA total of 49 differentially expressed circRNAs were found in the placental tissues of women with sPE. Several differentially expressed mRNAs were also observed in the sPE patients. KEGG analysis revealed that the most enriched pathway of the circRNAs was the MAPK signaling pathway, while the differentially expressed mRNAs were primary enriched in pathways in cancer. Among these circRNAs, hsa_circ_0001438, hsa_circ_0001326, and hsa_circ_32340 were upregulated in the sPE patients and the circRNA-miRNA-mRNA interaction network generated with these three circRNAs revealed a broad regulatory network that might be involved in the pathogenesis of sPE.ConclusioncircRNAs are differentially expressed in sPE. The upregulation of hsa_circ_0001438, hsa_circ_0001326, and hsa_circ_32340 has a potential role in the regulation of miRNA and mRNA expression. Changes to the expression profiles of the circRNAs might be linked to the pathogenesis of sPE and could function as biomarkers.