Characterization of microRNA Profiles in Pasteurella multocida-Infected Rabbits and Identification of miR-29-5p as a Regulator of Antibacterial Immune Response

Pasteurella multocida is the pathogenic agent for a variety of severe diseases in livestock, including rabbits. MicroRNAs (miRNAs) participate in the immune response to the pathogen. Distinct miRNA expression patterns were explored in rabbit lung by small-RNA deep sequencing to assess dysregulated miRNAs during P. multocida infection. Totally, 571 miRNAs were screened, of which, 62 were novel, and 32 exhibited differential expression (DE). Of the 32 known DE-miRNAs, 13 and 15 occurred at 1 day and 3 days post-infection (dpi); and ocu-miR-107-3p and ocu-miR-29b-5p were shared between the two time points. Moreover, 7,345 non-redundant target genes were predicted for the 32 DE-miRNAs. Putative target genes were enriched in diverse GO and KEGG pathways and might be crucial for disease resistance. Interestingly, upregulation of ocu-miR-29-5p suppresses P. multocida propagation and downregulates expression of epithelial membrane protein-2 (EMP2) and T-box 4 (TBX4) genes by binding to their 3′ untranslated region in RK13 cells. Thus, ocu-miR-29-5p may indirectly inhibit P. multocida invasion by modulating genes related to the host immune response, such as EMP2 and TBX4.

Network-Based Inference of Hub Genes In Epithelial Membrane Protein 2-Treated Human RPE cells

Backgrounds Identification of hub genes (HGs) using transcriptome data of human retinal pigment epithelial cells (hRPECs) samples treated with epithelial membrane protein 2 (EMP2) was helpful to accurately evaluate the functional relevance of genetic alterations in activity proteins (APs) in these cells. Results We performed differential expression genes (DEGs) analyses of public RNA-seq transcriptome data of EMP2 treated hRPECs, vector control (VC) and wild type (WT) hRPECs. VIPER (Virtual Inference of Protein activity by Enriched Regulon analysis) was used to convert DEGs outcomes to APs signatures and ARACNE (Algorithm for the Reconstruction of Accurate Cellular Networks) was used to construct transcription regulatory networks (TRNs) to identify hub genes (HGs). Conclusions In addition to identifying a significant fraction of DEGs among EMP2-OE groups and EMP-KD groups when compared to VC or WT groups, respectively, we also accurately inferred aberrant TGNs and found several HGs induced by EMP2-overexpressed hRPECs under hypoxia. Thus, we raised a hypothesis that EMP2 may regulate hRPECs angiogenesis via a PDGFA regulatory network, which would help to understand the complex biology of angiogenesis in EMP2 and hypoxia treated hRPECs.

Network-based Inference of Hub Genes in Epithelial Membrane Protein 2-treated Human RPE cells

BackgroundsIdentification of hub genes (HGs) using transcriptome data of epithelial membrane protein 2 (EMP2) treated human retinal pigment epithelial cells (hRPECs) samples was helpful to accurately evaluate the functional relevance of genetic alterations in activity proteins (APs) in these cells.ResultsWe performed differential expression genes (DEGs) analyses of public RNA-seq transcriptome data of EMP2 treated hRPECs, victor control (VC) and wild type (WT) hRPECs. VIPER (Virtual Inference of Protein activity by Enriched Regulon analysis) was used to convert DEGs outcomes to APs signatures and ARACNE (Algorithm for the Reconstruction of Accurate Cellular Networks) was used to construct transcription regulatory networks (TRNs) to identify hub genes (HGs). ConclusionsIn addition to identifying a significant fraction of DEGs among EMP2-OE groups and EMP-KD groups when compared to VC or WT groups, respectively, we also accurately inferred aberrant TGNs and found several HGs induced by EMP2-overexpressed hRPECs under hypoxia. Thus, we raise a hypothesis that EMP2 may regulate hRPECs angiogenesis via a PDGFA regulatory network, which would help to understand the complex biology of angiogenesis in EMP2 and hypoxia treated hRPECs.

Increased epithelial membrane protein 2 expression in glioblastoma after treatment with bevacizumab

Background Antiangiogenic therapy with bevacizumab has failed to provide substantial gains in overall survival. Epithelial membrane protein 2 (EMP2) is a cell surface protein that has been previously shown to be expressed in glioblastoma, correlate with poor survival, and regulate neoangiogenesis in cell lines. Thus, the relationship between bevacizumab and EMP2 was investigated. Methods Tumor samples were obtained from 12 patients with newly diagnosed glioblastoma at 2 time points: (1) during the initial surgery and (2) during a subsequent surgery following disease recurrence post-bevacizumab treatment. Clinical characteristics and survival data from these patients were collected, and tumor samples were stained for EMP2 expression. The IVY Glioblastoma Atlas Project database was used to evaluate EMP2 expression levels in 270 samples by differing histological areas of the tumor. Results Patients with high EMP2 staining at initial diagnosis had decreased progression-free and overall survival after bevacizumab (median progression-free survival 4.6 months vs 5.9 months; log-rank P = .076 and overall survival 7.7 months vs 14.4 months; log-rank P = .011). There was increased EMP2 staining in samples obtained after bevacizumab treatment in both unpaired (mean H-score 2.31 vs 1.76; P = .006) and paired analyses (mean difference 0.571; P = .019). This expression increase correlated with length of bevacizumab therapy (R2 = 0.449; Pearson P = .024). Conclusions Bevacizumab treatment increased EMP2 protein expression. This increase in EMP2 correlated with reduced mean survival time post-bevacizumab therapy. We hypothesize a role of EMP2 in clinical bevacizumab resistance and as a potential antiangiogenic therapeutic target in glioblastoma.