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Updated: Apr 30, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-138-5p inhibits WiT-49 cell growth in vitro by downregulating TCF3 expression, and suppresses tumorigenesis in
Zhigang Yao1,2, Nian Zhou3, Huangchenghao Zhang1
1Department of Urology Surgery, Kunming Children's Hospital, No. 288, Qianxing Road, Kunming, 650228, Yunnan, China.
Purpose:
miR-138-5p plays a tumor-suppressing role, but its function in Wilms tumor (WT) has not yet been explored. This study aimed to investigate the role of miR-138-5p in the progression of WT.
Methods:
Hematoxylin‒eosin staining was used to analyze histopathological changes in WT tissues and adjacent normal tissues. qPCR was used to detect the expression of miR-138-5p in WT tissues and cells. Immunohistochemical staining and qPCR were used to detect the expression of TCF3. The interaction between miR-138-5p and TCF3 was confirmed by correlation analysis, qPCR, and dual-luciferase assays, respectively. CCK-8, colony formation, Transwell, and wound-healing assays were performed to identify the effects of miR-138-5p and TCF3 on the proliferation and migration of WiT49 cells. A murine xenograft model was used to investigate the function of miR-138-5p on WT growth in vivo.
Results:
miR-138-5p was expressed at low levels in WT tissues and WiT-49 cells. Functional studies demonstrated that the upregulation of miR-138-5p markedly inhibited the proliferation, colony-formation capacity, and migratory/invasive potential of WiT-49 cells. Subsequently, the therapeutic potential of miR-138-5p overexpression was confirmed in murine xenograft models, which markedly inhibited tumor growth compared with that in the control group. TCF3 is a target of miR-138-5p, and its expression is negatively correlated with that of miR-138-5p. Furthermore, the results of rescue experiments indicated that the tumor-suppressing effects of miR-138-5p in WiT-49 cells were reversed by TCF3 overexpression.
Conclusions:
miR-138-5p could be a tumor suppressor that regulates the proliferation of WT cells by targeting and reducing TCF3 expression.
Insights
MicroRNA-138-5p (miR-138-5p) acts as a tumor suppressor in Wilms tumor (WT) by inhibiting cell proliferation and migration. It targets TCF3, suggesting miR-138-5p as a potential therapeutic target for WT.
Area of Science:
- Molecular Biology
- Oncology
Background:
- Wilms tumor (WT) is a pediatric kidney cancer with incompletely understood molecular mechanisms.
- MicroRNA-138-5p (miR-138-5p) is known to have tumor-suppressive functions in various cancers.
- The role of miR-138-5p in WT has not been previously investigated.
Purpose of the Study:
- To elucidate the function of miR-138-5p in the progression of Wilms tumor.
- To investigate the potential of miR-138-5p as a therapeutic agent in WT.
Main Methods:
- Histopathological analysis of WT tissues using Hematoxylin-Eosin staining.
- Quantitative PCR (qPCR) to assess miR-138-5p and TCF3 expression.
- In vitro assays (CCK-8, colony formation, Transwell, wound-healing) to evaluate cell proliferation and migration.
- In vivo studies using a murine xenograft model to assess tumor growth.
- Dual-luciferase assays to confirm the interaction between miR-138-5p and TCF3.
Main Results:
- miR-138-5p expression was significantly downregulated in WT tissues and cells.
- Overexpression of miR-138-5p suppressed WT cell proliferation, colony formation, and migration/invasion in vitro.
- miR-138-5p overexpression inhibited tumor growth in a murine xenograft model.
- TCF3 was identified as a direct target of miR-138-5p, with inverse correlation in expression.
- TCF3 overexpression rescued the tumor-suppressive effects of miR-138-5p.
Conclusions:
- miR-138-5p functions as a tumor suppressor in Wilms tumor.
- miR-138-5p inhibits WT cell proliferation and migration by targeting and downregulating TCF3 expression.
- miR-138-5p represents a potential therapeutic target for Wilms tumor treatment.
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