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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiRNA-134 suppresses esophageal squamous cell carcinoma progression by targeting FOXM1
Yuan Yuan1, Qian Wang2, Fangfang Cao1
1Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University Qingdao 266000, Shandong Province, People's Republic of China.
Abstract:
Previous studies showed that the dysregulation of miRNAs was closely associated with cancer progression. The aim of this study was to verify whether miR-134, miR-10a, miR-29c, miR-942, miR-93, and miR-218 could inhibit esophageal squamous cell carcinoma (ESCC) cell invasion and migration. ESCC tissue and normal esophageal tissue adjacent to carcinoma from patients (54 cases) undergoing surgery were collected. RT-PCR was used to test the expression of miR-134, miR-10a, miR-29c, miR-942, miR-93, and miR-218 in these tissues. In addition, western blot was applied to test the expression of MMP-2, MMP-9, COL1A1, COL1A5 and FOXM1. In the vitro experiment, EC9706 cells were transfected with miR-134 mimics, then wound healing was employed to test the migratory ability of EC9706 cells. Transwell chambers was used to test the invasion ability of cells. The expression of MMP-2, MMP-9, COL1A1, COL1A5, and FOXM1 waas detected by western blot. In order to confirm whether FOXM1-3'-UTR was the target gene of miR-134, we performed a luciferase assay. FOXM1 over-expression plasmid was transfected to further confirm miR-134 played its role by targeting FOXM1. Our results showed that the expression of miR-134 was decreased in the ESCC tissue compared with normal esophageal tissue, (P<0.01), but the expression of MMP-2, MMP-9, COL1A1, COL1A5 and FOXM1 were significantly increased (P<0.01). In an in vitro experiment, compared with the mimic control, the expression of MMP-2, MMP-9, COL1A1, COL1A5 and FOXM1 were decreased in the miR-134 mimic-transfected EC9706 cells (P<0.01). The migration and invasion activity of EC9706 cells was also decreased after transfection with miR-134 mimics (P<0.01). The luciferase activity of the FOXM1-3'-UTR plasmid was significantly suppressed by miR-134 (P<0.01). Overexpression of FOXM1 abrogated miR-134-mediated inhibition of EC9706 cell migration and invasion. In conclusion, miR-134 inhibited EC9706 cell migration and invasion by targeting FOXM1. miR-134 may be a novel treatment target for ESCC.
Insights
MicroRNA-134 (miR-134) inhibits esophageal squamous cell carcinoma (ESCC) cell invasion and migration by targeting FOXM1. This finding suggests miR-134 as a potential therapeutic target for ESCC treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA (miRNA) dysregulation is implicated in cancer progression.
- Esophageal squamous cell carcinoma (ESCC) is a significant global health concern.
- Specific miRNAs, including miR-134, are investigated for their roles in ESCC metastasis.
Purpose of the Study:
- To investigate the inhibitory effect of miR-134 on ESCC cell invasion and migration.
- To determine the relationship between miR-134 expression and key molecular targets in ESCC.
- To explore the potential of miR-134 as a therapeutic target for ESCC.
Main Methods:
- Quantitative real-time PCR (RT-PCR) to assess miRNA and gene expression in ESCC tissues.
- Western blot to analyze protein expression of MMP-2, MMP-9, COL1A1, COL1A5, and FOXM1.
- In vitro assays including wound healing and Transwell chambers to evaluate cell migration and invasion.
- Luciferase reporter assay and gene overexpression to confirm target interactions.
Main Results:
- miR-134 expression was significantly decreased in ESCC tissues compared to normal tissues.
- Expression of MMP-2, MMP-9, COL1A1, COL1A5, and FOXM1 was significantly increased in ESCC tissues.
- miR-134 mimics reduced ESCC cell migration, invasion, and expression of target genes in vitro.
- miR-134 directly targeted FOXM1, inhibiting its activity and downstream effects.
Conclusions:
- miR-134 suppresses ESCC cell migration and invasion by targeting the FOXM1 pathway.
- Restored miR-134 levels inhibit key proteins involved in extracellular matrix degradation and cell motility.
- miR-134 represents a promising novel therapeutic target for esophageal squamous cell carcinoma.
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