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Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
MicroRNA-139-5P inhibits human prostate cancer cell proliferation by targeting Notch1
Qian Sun1, Danhui Weng1, Kezhen Li1
1Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Abstract:
Despite an improvement in the efficacy of chemotherapeutic agents, the outcome of patients with prostate cancer remains poor. MicroRNA (miRNA/miR)-139 expression is often downregulated in multiple types of tumor, including in prostate cancer. The aim of the present study was to investigate the inhibitory effect of miR-139 on the PC-3, C4-2B and LNCaP prostate cancer cell lines. Analysis of the cell cycle of PC-3, C4-2B and LNCaP cells transfected with miR-139 revealed a significantly increased percentage of cells in the G1 phase and a decreased percentage in the S and G2 phases compared with those transfected with a negative control miRNA. The growth inhibitory rate of miR-139-transfected cells 24, 48 and 72 h after transfection were 32.83±2.61, 52.58±3.2 and 62.36±4.55% in PC-3 cells; 30.28±2.25, 51.74±3.27 and 60.80±3.58% in C4-2B cells; and 33.20±2.67, 51.83±3.59 and 61.79±4.85% in LNCaP cells, respectively. The present study revealed that miR-139 inhibited the proliferation of prostate cancer cells by interfering with the cell cycle. Further study into the mechanism by which this happened suggested that miR-139 reduced cyclin D1 expression and inhibited cell proliferation through targeting Notch1.
Insights
MicroRNA-139 (miR-139) inhibits prostate cancer cell growth by disrupting the cell cycle. This microRNA (miRNA) targets Notch1, reducing cyclin D1 expression and slowing proliferation in prostate cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer outcomes remain poor despite advances in chemotherapy.
- MicroRNA (miRNA/miR)-139 is frequently downregulated in various tumors, including prostate cancer.
- Understanding miR-139's role is crucial for developing novel prostate cancer therapies.
Purpose of the Study:
- To investigate the inhibitory effects of miR-139 on prostate cancer cell lines (PC-3, C4-2B, LNCaP).
- To analyze the impact of miR-139 on the cell cycle progression of prostate cancer cells.
- To elucidate the molecular mechanisms underlying miR-139's anti-proliferative action.
Main Methods:
- Prostate cancer cell lines (PC-3, C4-2B, LNCaP) were transfected with miR-139 mimics or a negative control miRNA.
- Cell cycle analysis was performed using flow cytometry.
- Cell proliferation rates were measured at 24, 48, and 72 hours post-transfection.
- Western blotting or similar techniques were used to assess protein expression (e.g., cyclin D1, Notch1).
Main Results:
- Transfection with miR-139 significantly increased the percentage of cells in the G1 phase and decreased those in the S and G2 phases.
- miR-139 demonstrated substantial growth inhibitory rates across all tested cell lines at 24, 48, and 72 hours.
- miR-139 was found to reduce cyclin D1 expression and target Notch1, thereby inhibiting cell proliferation.
Conclusions:
- miR-139 effectively inhibits the proliferation of prostate cancer cells by modulating cell cycle progression.
- The anti-proliferative effect of miR-139 is mediated through the downregulation of cyclin D1 and targeting of Notch1.
- miR-139 represents a potential therapeutic target for prostate cancer treatment.
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