Up-regulation of LINC01010 and lncRNA CASC15 can regulate the p53 signaling pathway and apoptosis process by regulation of PERP expression level as a breast cancer biomarker: Integrated systems biology and experimental approach

Abstract

Objectives The transmembrane protein PERP is present in numerous epithelial and epithelium-derived cells in tessellating junctions and other junctional and non-junctional plasma membrane regions. Previous research has focused on the involvement of the PERP gene and associated non-coding RNA regulators in developing several cancer types. In this study, we performed a high-throughput microarray data analysis and related interaction and pathway analysis to find novel genes in breast cancer and perform a qRT-PCR experiment to measure the accurate expression level of genes. Materials and method Microarray data analysis and gene set enrichment analysis (GSEA) were performed to find novel dysregulated genes in the breast cancer (BC) samples. Protein-protein interaction, pathway enrichment, gene ontology (GO), and RNA interaction analyses were performed to find an integrated regulation network. The qRT-PCR experiment was performed to evaluate the expression of found genes. Results According to the bioinformatics analyses, PERP, lncRNA CASC15, and LINC01010 were selected as the hub dysregulated genes in the BC samples, regulating the p53 signaling pathway. These genes were selected from a ceRNA network. PERP (logFC: 2.631, p-value: 0.006), lncRNA CASC15 (logFC: 2.627, p-value: 0.0018), and LINC01010 (logFC: 1.838, p-value: 0.0049) have up-regulation significantly in the BC samples. Also, CASC15 can be considered as a novel diagnostic biomarker of Isfahan BC (AUC: 0.7008, p-value: 0.0149). There were significant correlations between the expression of PERP and LINC01010 and age, menopausal and HER2 receptor statuses of Isfahan patients. Conclusion LINC01010 and CASC15 can regulate the expression level of PERP in the BC patients and change the normal regulation of the p53 signaling pathway and affect the apoptosis process of normal cells. CASC15 as a potential diagnostic biomarker and LINC01010 as a potential prognostic biomarker could regulate the BC development in the different ages, menopausal statuses, and HER2 receptor negative patients.