Identification of chemoresistance-associated microRNAs and hub genes in breast cancer using bioinformatics analysis.

Breast cancer threatens women's health. Although there are a lot of methods to treat breast cancer, chemotherapy resistance still hinders the effectiveness of treatment. This study attempts to explore the mechanism of chemotherapy resistance from the perspective of miRNA and look for several new targets for developing new drugs. Three datasets (GSE73736, GSE71142 and GSE6434) from Gene Expression Omnibus (GEO) were used for the bioinformatics analysis. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DE-genes) were obtained by using R package "limma". DAVID tool was used to perform gene ontology annotation analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the overlapping genes. Protein-protein interaction (PPI) network was established by STRING database and visualized by software Cytoscape. Hub genes were identified by software Cytoscape. The prognostic value of hub genes was assessed through Kaplan-Meier plotter website. In total, 22 DE-miRNAs, 1932 DE-genes and top 10 hub genes were obtained. The genes were mainly enriched in cell signaling pathways like ErbB signaling pathway and PI3K / AKT/mTOR pathway. These pathways have a significant impact on the proliferation, invasion and drug resistance in cancer. MiRNA-Gene interaction may provide new insight for exploring the mechanism of chemotherapy resistance in breast cancer. Our study ultimately identified effective biomarkers and potential drug targets, which may enhance the effect of chemotherapy in patients with breast cancer.

MRPL13 is a Prognostic Cancer Biomarker and Correlates with Immune Infiltrates in Breast Cancer.

OBJECTIVE: To study the expression of MRPL13 in breast cancer tissues using TCGA database, analyze the correlation between the expression and clinicopathological characteristics of patients, and explore the role of MRPL13 in the development of breast cancer (BC). METHODS: The BC mRNA data and clinical information were downloaded from TCGA database. The correlation between MRPL13 expression and clinicopathological parameters was analyzed. Cox regression multivariate analysis was used to explore the factors affecting the prognosis of BC patients. The UALCAN database was used to analyze the expression level of MRPL13 in BC and its relationship with clinical pathological factors. The GSEA method was used to predict the possible regulatory pathways of MRPL13. Immune responses of MRPL13 expression were analyzed using TISIDB and CIBERSORT. Additionally, GEPIA, K-M survival analysis and data from the HPA were used to validate the outcomes. RESULTS: The expression of MRPL13 in BC tissues was significantly higher than normal counterparts, patients with low MRPL13 expression had a better survival prognosis, also indicated an independent prognostic factor. GSEA analysis showed that the regulation of cell migration, positive regulation of endothelial cell migration, and Notch signaling pathway were enriched in tissues with low expression of MRPL13. Additionally, depleting MRPL13 expression inhibited invasion in MCF-10A and MCF-7 cells. Furthermore, PCR showed that MRPL13 affected VEGFA and MMP gene expression. CIBERSORT analysis revealed that the amount of NK cells decreased when MRPL13 expression was high. CONCLUSION: The expression of MRPL13 mRNA is upregulated in BC tissues, and the expression level of MRPL13 is significantly related to the clinicopathological factors of patients. High MRPL13 expression is a poor prognostic factor for BC, and it can be used as a molecular marker for prognosis judgment and as a potential therapeutic target.

Hierarchically Nanostructured Fe3O4/C Composite as a Promising Magnetic Targeted Drug Nanocarrier.

Nanostructured Fe3O4/C composites are very attractive for high-performance magnetic targeted drug carriers. Herein, Fe3O4/C composite nanospheres with good dispersity are prepared by a simple one-step hydrothermal synthesis and subsequent heat treatment in Ar. The composite nanospheres consist of clustered primary nanoparticles, and exhibit a hierarchical architecture with a high specific surface area of 119.3 m² g-1. The Fe3O4/C composite nanospheres show a high saturation magnetization value of 101 emu g-1 and good biocompatibility. In particular, the composite nanospheres deliver a large loading content (85.8%) of epirubicin hydrochloride (EPI), resulting from their unique composition and microstructure. More importantly, the release of EPI from the EPI-loaded magnetic carrier (Fe3O4/C-EPI) may be enhanced by both a slightly acidic environment and a rotating magnetic field induced by a simple motor-driven magnet system. The above favorable properties make the hierarchical Fe3O4/C composite sample a promising candidate for magnetic targeting nanocarriers of EPI.