Leila Gholami, Farnoosh Attari, Mahmood Talkhabi, Fatemeh Saadatpour,
Volume 10, Issue 1 (6-2023)
Abstract
Breast cancer is the most common cause of death from cancer among women. The triple-negative breast cancer (TNBC) is the most invasive subtype, and chemotherapy is the only therapy option. Cancer cells preferably utilize the glycolysis pathway even with proper oxygen availability, and this activation plays a great role in tumorigenesis. Therefore, glycolysis targeting can be an effective strategy for cancer treatment. Here, the apoptotic effect of a glycolysis inhibitor named dichloroacetate (DCA) on TNBC cells MDA-MB-231 was assessed, and the expression of anti-apoptotic genes and oncogenic miRNAs was evaluated. MTT assay showed that DCA reduces cell viability in a dose-dependent manner with the IC50 concentration of 50 mM. Annexin/PI assay demonstrated that DCA due to DCA treatment. Finally, the expression of anti-apoptotic genes Bcl2l1 and Mcl1 and oncogenic miRNAs miR21 and miR27a decreased due to DCA treatment. Our results confirmed that DCA, as a glycolysis inhibitor, leads to apoptosis induction in TNBC cells because of reducing expression of viability genes and miRNAs.
Laleh Mavaddatiyan, Mahmood Talkhabi,
Volume 11, Issue 3 (12-2024)
Abstract
Ferroptosis, as a type of newly recognized iron-dependent programmed cell death, is closely related to aging. The aim of this study is to investigate the role of ferroptosis in the aging of mesenchymal stem cells (MSCs). GSE97311 dataset (containing expression data of fetal and adult MSCs) was analyzed and differentially expressed genes (DEGs) were extracted. Then, among them, ferroptosis-related differentially expressed genes (FRDEGs) were determined. In the next step, biological functions, protein-protein interactions, hub genes, upstream regulators, and inflammatory factors related to FRDEGs were analyzed using different bioinformatics methods. According to the analysis, 34 genes were identified as FRDEGs. Analysis of biological functions showed that these genes are mostly involved in oxidoreductase activities, fatty acid synthesis and response to iron ion. Also, the analyzes related to the signaling pathways also showed that these genes are mostly involved in the pathways related to types of cancers as well as fatty acid biosynthesis. According to the analysis, miR-26b-5p was identified as the most important miRNA and LINC00205 and GAS5 as the most important lncRNAs. Hub genes including HMOX1, EZH2, NEDD4L, PTGS2, CDKN2A, ATF3, NOX4, TXNIP, SNCA and MAPK3 were identified as the main genes of ferroptosis related to aging of MSCs.