Human Protein Kinase C Alpha

Breast cancer (BC) is the most common cancer worldwide. However, the expression and potential mechanism of miR-375 in BC are still controversial. We first collected microRNA chips and microRNA sequencing data from multiple databases for analyzing the expression level of miR-375, and further exploring the target genes and underlying molecular mechanism in BC. miR-375 in BC was predominantly overexpressed compared with that in normal breast tissues (pooled standard mean difference [SMD] = 0.49; 95 % confidence interval [CI]: 0.24-0.73, p < 0.0001). Meanwhile, the overall pooled area under the curve (AUC) in the summary receiver operating characteristic (SROC) of miR-375 was 0.83 (95 % CI = 0.79-0.86) based on 2928 cases of BC patients and 816 cases of controls, while the diagnostic positive likelihood ratio (DLR) positive and the DLR negative value were 3.90 (95 % CI = 2.46-6.19) and 0.39 (95 % CI = 0.28-0.54), respectively. The hazard ratios (HRs) were 1.29 (95 % CI = 1.04-1.6, P = 0.02) and 1.23 (95 % CI = 0.89-1.7, P = 0.22) for the cohorts of METABRIC and The Cancer Genome Atlas (TCGA). In vitro study demonstrated that miR-375 inhibitor could suppress the cell growth and induce apoptosis of BC cells. A total of 107 overlapping genes from microarrays after miR-375 transfection, the TCGA RNA sequencing, the microarrays of Affymetrix platform, and online predicting software were selected as the prospective targets of miR-375 in BC. Based on Gene Ontology (GO) enrichment analysis, the potential targets of miR-375 were notable for their somatic stem cell division, plasma membrane, and proline-rich region binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination demonstrated that the targets were associated with the pathways of prion diseases, proteoglycans in cancer, and focal adhesion. Then, 107 targets of miR-375 in BC were used to construct a protein-protein interaction (PPI) network. Finally, EGFR, PRKCA, PPARA, ADIPOQ, and ITSN1 were found to be the hub genes of miR-375. These targets showed negative correlations with miR-375 level. The upregulated miR-375 might play an essential part in the tumorigenesis and progression of BC.

Objective: Viral hepatitis is associated with high morbidity and mortality. Identification of biological pathways involved in hepatic fibrosis resulting from chronic hepatitis C are essential for better management of patients. Constructing the HCV-human protein interaction network through bioinformatics may enable us to discover diagnostic biological pathways. We investigated to identify dysregulated pathways and gene enrichment based on actin alpha 2 (ACTA2) and glial fibrillar acidic protein (GFAP) interaction network analysis in hepatic fibrosis. Methods: This is an in-silico study conducted at Ziauddin University from March,2019 to September 2019. Enrichment and protein-protein interaction (PPI) network analysis of the identified proteins: GFAP and ACTA2 along with their mapped gene data sets was performed using FunRich version 3.1.3. Results: Biological pathway grouping showed enrichment of proteins (85.7%) in signalling pathway by epidermal growth factor receptor (EGFR) and Tumor growth factor (TGF)-beta Receptor followed by signaling by PDGF, FGFR and NGF (71.4%) (p < 0.001). SRC, PRKACA, PRKCA and PRKCD were enriched in both EGFR and TGF-beta Signalling pathways. Conclusion: EGFR and TGF-beta signalling pathways were enriched in liver fibrosis. SRC, PRKACA, PRKCA and PRKCD were enriched and differentially expressed in both EGFR and TGF-beta signalling pathways