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The effect of glycolysis inhibitor dichloroacetate on the apoptosis rate and alteration of gene and miRNA expression of breast cancer cells MDA-MB-231
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.

Identification of hub genes and their related microRNAs in triple negative breast cancer
Dr. Zohreh Jahanafrooz,
Volume 11, Issue 4 (2-2025)
Abstract
Breast cancer is the most frequently diagnosed cancer in women. Triple-negative breast cancer (TNBC) is a kind of breast cancer that does not have any of the receptors that are commonly found in breast cancer. This study aimed to evaluate differentially expressed genes (DEGs) and their related microRNAs (miRNAs) in TNBC. GSE113865 and GSE154255 were selected from GEO database. DEGs and differentially expressed miRNAs between normal and TNBC tissues were identified via GEO2R online tools and R program. STRING was used to construct a protein–protein interaction (PPI) network of DEGs. The hub genes, obtained using the cytoHubba plugin in Cytoscape. We used R program and Enrichr database to enrichment analysis of hub genes. Then intersection of predicted hub gene's miRNAs and differentially expressed miRNAs was investigated. UBE2C and SAA1 were the highest upregulated and downregulated genes, respectively. Six main hub genes were identified, including CDC20, DLGAP5, TPX2, UBE2C, TK1, and CDC45. All the mentioned genes were upregulated and enriched in cell cycle progression. Some hub genes such as TPX2, UBE2C, and TK1 were targeted by differentially expressed miRNAs (miR-3679 and miR-4530). In conclusion, knockdown of hub genes could be a targeted therapy for TNBC. 
 
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