MiR-200c restoration inhibits FOXP3 and metastatic spread in breast cancer: evidence from in vitro and in vivo models.
Metastatic breast cancer remains a leading cause of cancer-related mortality in women, often driven by molecular pathways that promote invasion and immune evasion. MicroRNA-200c (miR-200c) is a known tumor suppressor that inhibits epithelial-mesenchymal transition (EMT), while FOXP3, a transcription factor typically associated with regulatory T cells, is aberrantly expressed in breast cancer cells and may contribute to tumor progression. This study investigates whether targeting the miR-200c/FOXP3 axis can suppress metastasis in breast cancer.
Metastatic (MDA-MB-361, MDA-MB-468) and non-metastatic (MCF-7) breast cancer cell lines were transfected with miR-200c mimic or inhibitor. Cell proliferation, apoptosis, and invasion were assessed using MTT, Annexin V/PI staining, and transwell assays. FOXP3 mRNA and protein levels were quantified using qRT-PCR and immunohistochemistry. A metastatic mouse model was established via intracardiac injection of tumor cells, followed by treatment with miR-200c mimic, inhibitor, or Cisplatin.
MiR-200c overexpression significantly suppressed proliferation and invasion and enhanced apoptosis in metastatic cells. FOXP3 mRNA and protein expression were downregulated in mimic-treated cells and tissues, while miR-200c inhibition led to increased FOXP3 expression. In vivo, miR-200c mimic treatment reduced tumor burden and metastatic infiltration in the brain and lungs. A strong inverse correlation between miR-200c and FOXP3 was observed (r = - 0.82, p < 0.01).
MiR-200c restoration inhibits FOXP3 and suppresses metastatic progression in breast cancer. Targeting the miR-200c/FOXP3 axis presents a novel and promising therapeutic approach for advanced breast cancer.
Metastatic (MDA-MB-361, MDA-MB-468) and non-metastatic (MCF-7) breast cancer cell lines were transfected with miR-200c mimic or inhibitor. Cell proliferation, apoptosis, and invasion were assessed using MTT, Annexin V/PI staining, and transwell assays. FOXP3 mRNA and protein levels were quantified using qRT-PCR and immunohistochemistry. A metastatic mouse model was established via intracardiac injection of tumor cells, followed by treatment with miR-200c mimic, inhibitor, or Cisplatin.
MiR-200c overexpression significantly suppressed proliferation and invasion and enhanced apoptosis in metastatic cells. FOXP3 mRNA and protein expression were downregulated in mimic-treated cells and tissues, while miR-200c inhibition led to increased FOXP3 expression. In vivo, miR-200c mimic treatment reduced tumor burden and metastatic infiltration in the brain and lungs. A strong inverse correlation between miR-200c and FOXP3 was observed (r = - 0.82, p < 0.01).
MiR-200c restoration inhibits FOXP3 and suppresses metastatic progression in breast cancer. Targeting the miR-200c/FOXP3 axis presents a novel and promising therapeutic approach for advanced breast cancer.
Authors
El-Khazragy El-Khazragy, Alsolami Alsolami, Aref Aref, Hassan Hassan, Othman Othman
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