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Breast cancer (BC) is the most common cancer among women with high morbidity and mortality. Therefore, new research is still needed for biomarker detection. GSE101124 and GSE182471 datasets were obtained from the Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray classification (PAM50). The circRNA-miRNA-mRNA relationship was investigated using the Cancer-Specific CircRNA, miRDB, miRTarBase, and miRWalk databases. The circRNA–miRNA–mRNA regulatory network was annotated using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. The protein-protein interaction network was constructed by the STRING database and visualized by the Cytoscape tool. Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The Disease-Free Survival and Overall Survival analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study. We identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype. We conclude that hsa_circ_0000515/miR-486-5p/SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC subgroup of BC. [ABSTRACT FROM AUTHOR]

Objective: Acute myeloid leukemia (AML) is a lethal type of cancer associated with dysregulation of progenitor hematopoietic stem cell behavior and its incidence is, unfortunately, increasing. Although there are various applications in treatment, since most of them are insufficient in early diagnosis, treatment and new prognostic biomarkers should be investigated. Materials and Methods: In this study, three Gene Expression Omnibus (GEO) datasets Genomic Spatial Event (GSE); GSE94591, GSE116617, and GSE163386) were used to investigate dysregulated expressions of circular RNAs (circRNAs), and the GSE142699 and GSE142698 datasets were analyzed to detect dysregulated expressions of microRNAs (miRNAs) and mRNAs, respectively. Filtering was applied with p value <0.05, log2FC=0.5 (circRNA), and log2FC=1 (miRNA and mRNA) from the raw data analyzed using the limma R package (v.3.46.0). We investigated circRNA-miRNA-mRNA interactions using special tools including CSCDv2.0, circBank, miRTarBase, miRDB, multiMiR, miRWalk, DIANA-microT, TarBase, miRanda, and TargetScan. The pathway analysis was performed using KEGG and GO programs. The STRING database and Cytoscape tool were used to construct and view protein interaction. Hub gene analysis was constructed using the MCODE tool. We have utilized the GEPIA tool to determine the Overall Survival of the hub genes. Results: In our study, 4 circRNAs, 3 miRNAs, and 6 genes that may be closely related to AML were detected. Conclusion: According to our bioinformatics analysis results, hsa_circ_0012152/miR-199a-5p/HOXA9 axis could be more important in AML. Therefore, in vitro and in vivo investigations are recommended. [ABSTRACT FROM AUTHOR]

Single-cell transcriptomics studies have begun to identify breast epithelial cell and stromal cell specific transcriptome differences between BRCA1/2 mutation carriers and non-carriers. We generated a single-cell transcriptome atlas of breast tissues from BRCA1, BRCA2 mutation carriers and compared this single-cell atlas of mutation carriers with our previously described single-cell breast atlas of healthy non-carriers. We observed that BRCA1 but not BRCA2 mutations altered the ratio between basal (basal-myoepithelial), luminal progenitor (luminal adaptive secretory precursor, LASP), and mature luminal (luminal hormone sensing) cells in breast tissues. A unique subcluster of cells within LASP cells is underrepresented in case of BRCA1 and BRCA2 mutation carriers compared with non-carriers. Both BRCA1 and BRCA2 mutations specifically altered transcriptomes in epithelial cells which are an integral part of NFκB, LARP1, and MYC signaling. Signaling pathway alterations in epithelial cells unique to BRCA1 mutations included STAT3, BRD4, SMARCA4, HIF2A/EPAS1, and Inhibin A signaling. BRCA2 mutations were associated with upregulation of IL6, PDK1, FOXO3, and TNFSF11 signaling. These signaling pathway alterations are sufficient to alter sensitivity of BRCA1/BRCA2-mutant breast epithelial cells to transformation as epithelial cells from BRCA1 mutation carriers overexpressing hTERT + PIK3CAH1047R generated adenocarcinomas, whereas similarly modified mutant BRCA2 cells generated basal carcinomas in NSG mice. Thus, our studies provide a high-resolution transcriptome atlas of breast epithelial cells of BRCA1 and BRCA2 mutation carriers and reveal their susceptibility to PIK3CA mutation-driven transformation., Significance: This study provides a single-cell atlas of breast tissues of BRCA1/2 mutation carriers and demonstrates that aberrant signaling due to BRCA1/2 mutations is sufficient to initiate breast cancer by mutant PIK3CA., (© 2024 The Authors; Published by the American Association for Cancer Research.)