Integrated analyses of long noncoding RNAs and mRNAs in the progression of breast cancer

Objective The objective was to explore the expression and potential functions of long noncoding RNA (lncRNA) and mRNAs in human breast cancer (BC). Methods Differentially expressed lncRNAs and mRNAs were identified and annotated in BC tissues by using the Agilent human lncRNA assay (Agilent Technologies, Santa Clara, CA, USA) and RNA sequencing. After identification of lncRNAs and mRNAs through quantitative reverse transcription polymerase chain reaction, we conducted a series of functional experiments to confirm the effects of knockdown of one lncRNA, TCONS_00029809, on the progression of BC. Results We discovered 238 lncRNAs and 200 mRNAs that were differentially expressed in BC tissues and para-carcinoma tissue. We showed that differentially expressed mRNAs were related to biological adhesion and biological regulation and mainly enriched in cytokine-cytokine receptor interaction, metabolic pathways, and PI3K-Akt signaling pathway. We created a protein–protein interaction network to analyze the proteins enriched in these pathways. We demonstrated that silencing of TCONS_00029809 remarkably inhibited proliferation, invasion, and migration of BC cells, and accelerated their apoptosis. Conclusions We identified a large number of differentially expressed lncRNAs and mRNAs, which provide data useful in understanding BC carcinogenesis. The lncRNA TCONS_00029809 may be involved in the development of BC.

Effects of Simulated Microgravity on the Physiology of Stenotrophomonas maltophilia and Multiomic Analysis

Many studies have shown that the space environment plays a pivotal role in changing the characteristics of conditional pathogens, especially their pathogenicity and virulence. However, Stenotrophomonas maltophilia, a type of conditional pathogen that has shown to a gradual increase in clinical morbidity in recent years, has rarely been reported for its impact in space. In this study, S. maltophilia was exposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14days, while the control group was exposed to the same bioreactors in a normal gravity (NG) environment. Then, combined phenotypic, genomic, transcriptomic, and proteomic analyses were conducted to compare the influence of the SMG and NG on S. maltophilia. The results showed that S. maltophilia in simulated microgravity displayed an increased growth rate, enhanced biofilm formation ability, increased swimming motility, and metabolic alterations compared with those of S. maltophilia in normal gravity and the original strain of S. maltophilia. Clusters of Orthologous Groups (COG) annotation analysis indicated that the increased growth rate might be related to the upregulation of differentially expressed genes (DEGs) involved in energy metabolism and conversion, secondary metabolite biosynthesis, transport and catabolism, intracellular trafficking, secretion, and vesicular transport. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the increased motility might be associated the upregulation of differentially expressed proteins (DEPs) involved in locomotion, localization, biological adhesion, and binding, in accordance with the upregulated DEGs in cell motility according to COG classification, including pilP, pilM, flgE, flgG, and ronN. Additionally, the increased biofilm formation ability might be associated with the upregulation of DEPs involved in biofilm formation, the bacterial secretion system, biological adhesion, and cell adhesion, which were shown to be regulated by the differentially expressed genes (chpB, chpC, rpoN, pilA, pilG, pilH, and pilJ) through the integration of transcriptomic and proteomic analyses. These results suggested that simulated microgravity might increase the level of corresponding functional proteins by upregulating related genes to alter physiological characteristics and modulate growth rate, motility, biofilm formation, and metabolism. In conclusion, this study is the first general analysis of the phenotypic, genomic, transcriptomic, and proteomic changes in S. maltophilia under simulated microgravity and provides some suggestions for future studies of space microbiology.

Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.

Identification of specific biomarkers and pathways in the synovial tissues of patients with osteoarthritis in comparison to rheumatoid arthritis

Osteoarthritis and rheumatoid arthritis are two common arthritis with different pathogenesis. Here, we explore the difference of genes and biological pathways in human synovial fibroblasts by using a bioinformatics method to clarify their potential pathogenesis. The GSE7669 dataset was originally produced by using an Affymetrix Human Genome U95 platform. We used the KEGG and GO analysis to identify the functional categories and pathways. Our results suggested that biological adhesion and cell adhesion are the main signaling pathways in osteoarthritis in comparison to rheumatoid arthritis. Furthermore, Albumin, MAPK3, PTPRC, COL1A1, and CXCL12 may be key genes in osteoarthritis. Therefore, our study provides potential targets for the specific and accurate therapy of osteoarthritis.

Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. In the current study, we aimed to unveil its role in glioma based on transcriptome level. Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA mRNA microarray dataset and 697 from TCGA RNA sequencing dataset, were downloaded and analyzed. R language was used to perform statistical analyses and generate figures. In glioma, CALU expression seemed to be positively associated with WHO grade system, and was enriched in IDH wildtype, mesenchymal and classical subtype. Genes that tightly correlated with CALU were screened and annotated with Gene Ontology, and it turned out that, these genes were highly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. Subsequent GSEA analysis further validated the profound involvement of CALU in EMT. To get further understanding of the association between EMT and CALU, GSVA analysis was performed to identify the EMT signaling pathways that CALU might involve. CALU expression was found to be positively correlated with TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, Pearson correlation indicated that CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug and TWIST1, in both CGGA and TCGA dataset. Kaplan-Meier curves and Cox regression analyses showed that higher CALU predicted a worse survival for patients, and the prognostic value was independent of WHO grade and age. In conclusion, CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently for glioma patients.

Shape effects in biological adhesion of ellipsoidal cells

Blood platelet adhesion is crucial for arterial thrombosis and hemostasis. The attachment of platelets to the injuries takes place under the action of high hydrodynamic forces and relies on the formation of breakable ligand-receptor bonds between the cell and the adhesive substrate. In this work we study how the geometrical effects may change the adhesive forces that stick platelets to the wounds. The mathematical model shows that oblate cells with high aspect ratio are more favourable for thrombus growth.

“Biological Adhesion” is a Significantly Regulated Molecular Process during Long-Term Primary In Vitro Culture of Oviductal Epithelial Cells (Oecs): A Transcriptomic and Proteomic Study

Oviductal epithelial cells (OECs) actively produce stimulating and protecting factors, favoring survival and viability of gametes and early embryos. The oviduct participates in the initial reproductive events, which strongly depends on adhesion. The analysis of differential gene expression in OECs, during long-term in vitro culture, enables recognition of new molecular markers regulating several processes, including “biological adhesion”. Porcine oviducts were stained with hematoxylin and eosin, as well as with antibodies against epithelial markers. Then, OECs were long-term in vitro cultured and after 24 h, 7, 15, and 30 days of culture were subjected to transcriptomic and proteomic assays. Microarrays were employed to evaluate gene expression, with Matrix-assisted laser desorption/ionization-time of light (MALDI-TOF) mass spectrometry applied to determine the proteome. The results revealed proper morphology of the oviducts and typical epithelial structure of OECs during the culture. From the set of differentially expressed genes (DEGs), we have selected the 130 that encoded proteins detected by MALDI-TOF MS analysis. From this gene pool, 18 significantly enriched gene ontology biological processes (GO BP) terms were extracted. Among them we focused on genes belonging to “biological adhesion” GO BP. It is suggested that increased expression of studied genes can be attributed to the process of intensive secretion of substances that exhibit favorable influence on oviductal environment, which prime gametes adhesion and viability, fertilization, and early embryo journey.