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Updated: Oct 27, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-133a-5p suppresses gastric cancer through TCF4 down-regulation
Mu-Qun He1, Jian-Feng Wan1, Hong-Fu Zeng1
1Department of Medical Oncology, FuJian Medical University Cancer Hospital, FuJian Cancer Hospital, Fuzhou, China.
Background:
The effect of microRNAs (miRNA) on cancer regulations has received a considerable amount of attention recently. MiR-133a-5p has been identified as an anti-tumor miRNA in several types of cancers. However, the effect of miR-133a-5p on gastric cancer (GC) have not been uncovered. In this study, we sought to evaluate the regulation of TCF4 expression by miR-133-5p and the role of the miR-25-3p/TCF4 axis in the progression of GC, with the aim of identifying a potential therapeutic target for GC.
Methods:
TCGA (The Cancer Genome Atlas), GTEx (The Genotype-Tissue Expression) and GEO (Gene Expression Omnibus) database were used to analyze the expression and prognosis. We performed MTT and EdU assays to elucidate the effect on cell replication. Apoptotic cells were stained with annexin V-fluorescein isothiocyanate and propidium iodide to stain, and then analyzed by flow cytometry. The effect on cell metastasis was investigated in wound healing and transwell assays. A dual-luciferase reporter assay was used to check for the direct targeting of TCF4 by miR-133a-5p. Bioinformatic analysis of the relationship of TCF4 with tumor microenvironment and the signaling cascade of TCF4 was finally performed.
Results:
We found that the level of miR-133a-5p was decreased in both tumor tissues and GC cell lines. MiR-133a-5p inhibited cell growth and metastasis, but promoted cell apoptosis. MiR-133a-5p directly targeted TCF4 and downregulated its expression. TCF4 was highly expressed in tumor and higher level of TCF4 indicated poorer prognosis. Moreover, TCF4 overexpression reversed the aforementioned anti-tumor activity of miR-133a-5p. The expression level of TCF4 was significantly correlated with tumor-infiltrating immune cells.
Conclusions:
Our findings altogether reveal that miR-133a-5p can serve as a tumor suppressor in gastric cancer via the miR-133a-5p/TCF4 pathway.
Insights
MicroRNA-133a-5p acts as a tumor suppressor in gastric cancer by inhibiting TCF4 expression. This pathway, involving miR-133a-5p and TCF4, offers a potential therapeutic target for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play a crucial role in cancer regulation.
- MiR-133a-5p is recognized as an anti-tumor miRNA in various cancers.
- The specific role of miR-133a-5p in gastric cancer (GC) remains largely unexplored.
Purpose of the Study:
- To investigate the regulatory relationship between miR-133a-5p and TCF4 expression in gastric cancer.
- To elucidate the function of the miR-133a-5p/TCF4 axis in gastric cancer progression.
- To identify potential therapeutic targets for gastric cancer.
Main Methods:
- Utilized TCGA, GTEx, and GEO databases for expression and prognosis analysis.
- Performed MTT, EdU, flow cytometry, wound healing, and transwell assays to assess cell proliferation, apoptosis, and metastasis.
- Conducted dual-luciferase reporter assays to confirm direct targeting of TCF4 by miR-133a-5p.
- Analyzed TCF4's association with the tumor microenvironment and signaling pathways via bioinformatics.
Main Results:
- Decreased miR-133a-5p levels were observed in gastric cancer tissues and cell lines.
- MiR-133a-5p suppressed cell growth and metastasis while promoting apoptosis.
- MiR-133a-5p directly targets and downregulates TCF4 expression.
- High TCF4 expression correlated with poorer prognosis and was linked to tumor-infiltrating immune cells.
- TCF4 overexpression counteracted the anti-tumor effects of miR-133a-5p.
Conclusions:
- MiR-133a-5p functions as a tumor suppressor in gastric cancer.
- The miR-133a-5p/TCF4 pathway is a key mechanism in gastric cancer progression.
- This pathway represents a promising therapeutic target for gastric cancer.
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