Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

Genetic and molecular heterogeneity,together with intrinsic and acquired resistance to therapy,represent the major obstacles to the successful treatment of different types of breast carcinoma.Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade,poor prognosis,and therapy resistance.Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas,and these genes are recognized as potential antitumor targets.Our aim was to evaluate the effect of retinoic acid(RA),a well-known cyto-differentiating agent,on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes.By applying various experimental approaches,we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines.We have shown that RA inhibits cell growth,reduces the number of Ki-67 positive cells,and causes cell-cycle arrest.RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression,including a higher decrease in cell viability,reduction in colony formation,and significant remodeling of cellular structure.We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines.By functional analysis,we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2,pointing to a SOX2-independent mechanism of action.The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders.Together,our study shows that the response of breast carcinoma cell lines to RA treatment may vary,highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.

Differentially expressed genes analysis and target genes prediction of miR-22 in breast cancer

Objective miR-22 is highly active in breast cancer, especially in the luminal B and HER2 subtypes.However, the detailed potential of the use of target genes for miR-22 in breast cancer are still unclear. Inthis study, we aimed to discover potential genes and the miRNA-DEGs network of miR-22 in breast cancerusing bioinformatics approaches.Methods Analysis of microarray data GSE17508 (including 3 miR-22 knockout samples and 3 controls)obtained from the Gene Expression Omnibus (GEO) database was performed. Differentially expressedgenes (DEGs) between the miR-22 knockout samples and the three control samples were detected usingGEO2R. The gene ontology (GO) functional enrichment analysis and protein-protein interaction (PPI)network of DEGs were performed using the online tool Metascape and STRING database, separately. ThemiR-22 and DEG networks were obtained from the miRNet database. Cytoscape software was used toconstruct and analyze a merged miRNA-DEG network. The online tools database, mirDIP 4.1, was used topredict miR-22 target genes.Results Certain DEGs and miRNAs may be potential targets for predicting and treating miR-22 expressedbreast cancer.Conclusion We constructed a prognostic model of rectal adenocarcinomas based on four immunerelatedlncRNAs by analyzing the data based on TCGA database, with high prediction accuracy. We alsoidentified two biomarkers with poor prognosis (PXN-AS1 and AL158152.2) and one biomarker with goodprognosis (LINC01871).