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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Function of microRNA‑141 in human breast cancer through cytotoxic CD4+ T cells regulated by MAP4K4 expression
Qing Zhang1, Huang Xin1, Tang Fen1
1Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Abstract:
The present study investigated the anti‑cancer effect of microRNA (miRNA)‑141 on apoptosis rate of breast cancer cells and the possible underlying mechanism. In patients with breast cancer, the expression of miRNA‑141 was downregulated. Overexpression of miRNA‑141 reduced breast cancer cell growth, inhibited the expression of cyclooxygenase‑2 (COX‑2), prostaglandin E2 (PGE2) and tumor necrosis factor (TNF)‑α, and increased the expression levels of interleukin (IL)‑10. However, downregulation of miRNA‑141 resulted in upregulation of COX‑2, PGE2 and TNF‑α expression levels, and an inhibition of IL‑10. Overexpression of miRNA‑141 suppressed mitogen‑activated protein kinase kinase kinase kinase 4 (MAP4K4) protein expression. Downregulation of miRNA‑141 markedly upregulated MAP4K4 protein expression in MCF‑7 cells. Promotion of MAP4K4 protein expression reduced the effects of miRNA‑141 on the toxicity of CD4+ T cells on breast cancer cells. The results of the present study indicated that miRNA‑141 may cause anti‑tumor effects in human breast cancer cells via cytotoxic CD4+ T cells.
Insights
MicroRNA-141 exhibits anti-cancer properties by promoting breast cancer cell apoptosis. Upregulating microRNA-141 may offer a therapeutic strategy against breast cancer by enhancing CD4+ T cell toxicity.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Breast cancer is a leading cause of mortality worldwide.
- MicroRNA-141 (miRNA-141) is frequently downregulated in breast cancer patients.
- Understanding miRNA-141's role is crucial for developing novel breast cancer therapies.
Purpose of the Study:
- To investigate the anti-cancer effects of miRNA-141 on breast cancer cell apoptosis.
- To elucidate the underlying molecular mechanisms of miRNA-141's action.
- To explore the relationship between miRNA-141, inflammatory markers, and immune cell activity.
Main Methods:
- Assessing miRNA-141 expression levels in breast cancer.
- Manipulating miRNA-141 expression (overexpression and downregulation) in breast cancer cell lines (MCF-7).
- Measuring apoptosis rates, inflammatory markers (COX-2, PGE2, TNF-α, IL-10), MAP4K4 protein expression, and CD4+ T cell toxicity.
Main Results:
- Downregulation of miRNA-141 observed in breast cancer patients.
- miRNA-141 overexpression reduced cell growth, inhibited COX-2, PGE2, TNF-α, and increased IL-10.
- miRNA-141 suppressed MAP4K4 expression, which in turn enhanced CD4+ T cell-mediated breast cancer cell toxicity.
Conclusions:
- miRNA-141 demonstrates significant anti-tumor effects in human breast cancer cells.
- The anti-cancer mechanism involves modulation of inflammatory pathways and MAP4K4 expression.
- miRNA-141 enhances anti-tumor immunity via cytotoxic CD4+ T cells, suggesting therapeutic potential.
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