lncRNA DSCAM-AS1 regulates the P13K-AKT and Ras/Raf/ERK signaling pathway correlated to EPCAM in the breast cancer patients: integrated systems biology and bioinformatics investigation
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Mahdieh Bakhshayesh,1 Parisa Rabiei Chamgordani,2 Mohammad Rezaei,3 Mansoureh Azadeh,4,*
1. Zist Fanavari Novin Biotechnology Institute
2. Zist Fanavari Novin Biotechnology Institute
3. Zist Fanavari Novin Biotechnology Institute
4. Zist Fanavari Novin Biotechnology Institute
- Introduction: Breast cancer is the most common cancer and the leading cause of death among women1. The snail is a crucial regulator of tumor cells' epithelial-mesenchymal transmission (EMT). Several studies have shown that nuclear snail expression is an adverse prognostic factor in human cancer2. Differential expression analysis was performed on the microarray datasets to find significant irregular genes in breast cancer cell line MCF.7. In this study, 54,675 genes were analyzed. After performing the Limma closed linear model on expression data, 5239 low-expression genes and 4697 high-expression genes were identified in this study, which was selected for bioinformatics and subsequent experimental research. This analysis illustrated that mRNAs have a single local base-pairing interaction, miRNA interaction analysis revealed that could regulate the expression of mRNA and lncRNA in an interaction axis, and we also show strong interactions between miRNA and lncRNA and selected genes.
- Methods: GSE58252 dataset Affymetrix was chosen and analyzed to find differentially expressed genes (DEGs) in BC samples compared to control samples. The GEO online database was used to find this dataset. The limma was used to conduct the DEG analysis. 6 samples were evaluated (3 controls and 3 patient BC samples). The genes with logFC > 2 & logFC < -2 are considered as the differentially expressed genes (DEGs) in this dataset. The adjusted p-value (adj. P. Value) < 0.001 is considered as the statistical significance level. The miRWalk was used to analyze miRNA–mRNA interactions. The Pathway enrichment analysis was carried out using KEGG and Reactome's online databases. All miRNAs were regained from DIANA-TarBase v7.0. The expression of lncRNAs in different tissues has been examined by the lnCAR databases. I was comparing the expression of genes in Breast cancer by Gepia2 databases—the protein-protein interaction analysis by STRING online software.
- Results: We examined three genes including KRAS, EPCAM, and DSCAM_AS1 (logFC > 2 & logFC < -2, adjusted p-value (adj. P. Value < 0.001) is considered as the statistically significance level. we found that mRNA EPCAM and DSCAM_AS1 lncRNA expression was increased, and mRNA KRAS decreased in tumor tissue from breast cancer patients compared to healthy patients. DSCAM-AS1 has significant direct interactions with the KRAS and EPCAM mRNA in Breast cancer cell line MCF.7. KRAS and EPCAM had several significant interactions that Played an important role in regulating cell proliferation. Interaction analysis of EPCAM, KRAS mRNA, and DSCAM_AS1 lncRNA illustrated that these RNAs have a single local base-pairing interaction (Energy = -36.43 kcal/mol) and (Energy = -12.01 kcal/mol). miRNA interaction analysis revealed that hsa-miR-373-3p could regulate the expression of EPCAM and LINC01018 lncRNA in an interaction axis. In addition, hsa-miR-183-5p could regulate the expression of KRAS and ADAM1A lncRNA in an interaction axis. KRAS could regulate the following signaling pathways: Ras, Breast cancer, Proteoglycans, MicroRNAs signaling pathway in cancer in cancer.
- Conclusion: KRAS, EPCAM, DSCAM_AS1 could be three prognostic biomarkers. lncRNA DSCAM_AS1 expression level has a significant positive correlation with the expression of KRAS and EPCAM in breast cancer; KRAS plays a role in the RAS protein in the MCF.7 cell line in breast cancer in the MAPK signaling pathway, which plays an essential role in proliferation furthermore in P13K_AKT signaling pathway can regulate the CELL proliferation Angiogenesis DNA repair. EPCAM knockdown led to decreased phosphorylation of Raf and ERK, suppression of malignant behavior of breast cancer cells, and inhibition of the Ras/Raf/ERK signaling pathway3.
- Keywords: Breast cancer, Snail, EPCAM, KRAS, MCF-7, DSCAM_AS1
