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Updated: Oct 16, 2026
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
Published on: March 31, 2015
miR-140-5p alleviates the aggressive progression of Wilms' tumor through directly targeting TGFBR1 gene
Hailei Wang1, Chunyan Lou1, Na Ma2
1Department of Pediatrics, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
Background And Objective:
Although many miRNAs are identified to be deregulated and play vital roles in the progression of Wilms' tumor (WT), there are still a large number of miRNAs are waiting for us to explore. The purpose of the present study is to investigate the different expressing profiles of miRNAs in WT tissues and the adjacent normal tissues, and probe the effects and mechanism of a certain miRNA among the different expressing miRNAs.
Methods:
miRNA microarray was recruited to assess the differently expressed miRNAs in WT tissues and normal tissues, which was further verified by RT-PCR. Receiver operating characteristic curves were performed to calculate the specificity and sensitivity of miRNAs in the diagnose of WT. CCK-8, flow cytometry, wound healing, transwell chamber and tumor-burdened assays were used to assess cell growth, apoptosis, migration, invasion and tumorigenesis. Luciferase report assay was used to evaluate the interaction between miR-140-5p and TGFBR1.
Results:
A total of 34 miRNAs were abnormally expressed in the WT tissues, among which, miR-140-5p was identified to be obviously down-regulated in WT tissues, and the AUC of it was 0.961. Besides, we found that patients with miR-140-5p low expression always had a shorter overall survival and more aggressive clinical features, such as bigger tumor size (P=0.002), higher pathological stage (P=0.003) and higher occurrence rate of lymph node metastasis (P=0.009) than those in patients with miR-140-5p high expression. Moreover, luciferase reporter assay showed that TGFBR1 was the direct target of miR-140-5p, which was negatively regulated by miR-140-5p and was highly expressed in WT tissues. Furthermore, knockdown of miR-140-5p obviously enhanced the proliferation and tumorigenesis and repressed the apoptosis of G401 cells, and these effects were all abolished when TGFBR1 was down-regulated.
Conclusion:
The present study illustrates that miR-140-5p functions as a tumor suppressor in the occurrence and development of WT via targeting TGFBR1, which provides theoretical foundation for serving miR-140-5p as a new diagnosis marker even a therapeutic target for WT.
Insights
This study reveals that miR-140-5p acts as a tumor suppressor in Wilms' tumor (WT) by targeting TGFBR1. Its downregulation correlates with aggressive WT features, suggesting potential as a diagnostic marker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wilms' tumor (WT) progression involves numerous deregulated microRNAs (miRNAs).
- Further exploration of miRNA roles in WT is crucial for understanding disease mechanisms.
Purpose of the Study:
- To identify differentially expressed miRNAs in WT tissues compared to adjacent normal tissues.
- To investigate the functional role and underlying mechanism of a specific dysregulated miRNA in WT.
Main Methods:
- miRNA microarray and RT-PCR for differential expression analysis.
- ROC curve analysis for diagnostic potential.
- Cellular assays (CCK-8, flow cytometry, wound healing, Transwell) for proliferation, apoptosis, migration, and invasion.
- Luciferase reporter assay to validate miRNA-target interaction.
Main Results:
- 34 miRNAs were deregulated in WT; miR-140-5p was significantly downregulated.
- Low miR-140-5p expression correlated with shorter survival, larger tumor size, advanced stage, and lymph node metastasis.
- TGFBR1 was identified as a direct target of miR-140-5p, negatively regulated and highly expressed in WT.
- miR-140-5p knockdown promoted proliferation and tumorigenesis while inhibiting apoptosis; these effects were reversed by TGFBR1 downregulation.
Conclusions:
- miR-140-5p acts as a tumor suppressor in Wilms' tumor development by targeting TGFBR1.
- miR-140-5p holds potential as a novel diagnostic marker and therapeutic target for WT.
