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Figure 4 | Breast Cancer Research

Figure 4

From: miR-24-2 controls H2AFX expression regardless of gene copy number alteration and induces apoptosis by targeting antiapoptotic gene BCL-2: a potential for therapeutic intervention

Figure 4

miR-24-2 overexpression and its effect on gene expression and cell proliferation. (a) Effect of miR-24-2 upregulation on gene expression profile of MCF-7 cells for TP53, ATM, P21, MDM2, CHEK2, H2AFX, CYT-C, BCL-2, BRCA1 and BRCA2. (b) miR-24-2 overexpressing MCF-7 cells treated with cisplatin (200 ╬╝mol/l) and assayed for apoptotic cell death using annexin V staining and fluorescence-activated cell sorting analysis. (c) miR-24-2-overexpressing MCF-7 cells treated with H2O2 (25 mmol/l) and analyzed for apoptosis. (1) Negative control (unstained MCF-7 cells), (2) MCF-7 control cells, (3) MCF-7 + mock transfection, (4) MCF-7 + miR-24-2 transfection, (5) MCF-7 + H2O2/cisplatin, (6) MCF-7 + mock transfection + H2O2/cisplatin and (7) MCF-7 + miR-24-2 transfection + H2O2/cisplatin. The extent of apoptosis was quantified as percentage of annexin V-positive cells. Error bars indicate standard deviation. (d) Luciferase expression in MCF-7 cells overexpressing miR-24-2 and transfected with pGL3 control vector or vector harboring the predicted miR-24-2 binding site present in 3'UTR of H2AFX/BCL-2 genes. (e) Proposed model of miR-24-2-mediated apoptotic induction. Following overexpression of miR-24-2, the mRNA expression of key apoptotic (BCL-2 and MDM2)/DNA damage response genes (H2AFX and P21) is downregulated. While downregulation of H2AX would lead to impaired DNA repair and loss of cell-cycle arrest, reduced expression of p21 prevents entry into cycle arrest pathway and instead signals the apoptotic pathway. Reduced BCL-2 and MDM2 expression is capable of directly inducing the apoptotic pathways leading to cell death.

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