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Published on: November 16, 2011
miR-133b Suppresses Invasion and Migration of Gastric Cancer Cells via the COL1A1/TGF-β Axis
Yuan Guo1, Guochun Lu1, Huahui Mao1
1Department of General Surgery, First People's Hospital of Tonglu, Hangzhou 311500, People's Republic of China.
Objective:
The study aimed to explore the mechanism of miR-133b regulating the invasion and migration of gastric cancer (GC) cells via the COL1A1/TGF-β axis.
Methods:
The miRNA expression profiles of GC downloaded from TCGA database were subjected to differential analysis to determine the target miRNA of interest, and the target genes of the miRNA were predicted by bioinformatics. GSEA was used for gene enrichment analysis. qRT-PCR was carried out to detect gene expression in GC cells. The effect of miR-133b on GC cells was examined by CCK-8, wound healing and Transwell assays. Western blot was conducted to assess the protein expression of EMT-related proteins. The binding relationship between genes was verified by dual-luciferase reporter gene assay.
Results:
The expression of miR-133b was markedly downregulated in GC tissue, while that of COL1A1 was upregulated. Overexpression of miR-133b decreased the migration and invasion of GC cells, and the EMT process was inhibited as well, while inverse results were observed when miR-133b was silenced. COL1A1 was a target gene of miR-133b and its overexpression had a significant impact on the prognosis of patients. GSEA pathway enrichment results showed that COL1A1 was markedly enriched in the TGF-β signaling pathway. In addition, COL1A1 overexpression induced the activation of the TGF-β signaling pathway to promote proliferation and migration of GC cells, whereas miR-133b overexpression suppressed the signaling pathway. Thus, overexpression of miR-133b and COL1A1 simultaneously would reverse the inhibitory effect of miR-133b on cell invasion and migration.
Conclusion:
In this study, miR-133b was found to inhibit the invasion and migration of GC cells via the COL1A1/TGF-β axis, which provides a new research direction for the diagnosis and targeted therapy of GC.
Insights
MicroRNA-133b (miR-133b) inhibits gastric cancer (GC) cell invasion and migration by targeting COL1A1 and suppressing the TGF-β pathway. This finding offers new avenues for GC diagnosis and targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) remains a significant global health challenge.
- Understanding the molecular mechanisms underlying GC cell invasion and migration is crucial for developing effective therapies.
Purpose of the Study:
- To elucidate the regulatory role of miR-133b in gastric cancer cell invasion and migration.
- To investigate the involvement of the COL1A1/TGF-β signaling axis in miR-133b-mediated GC progression.
Main Methods:
- Bioinformatic analysis of TCGA database for miRNA and gene expression profiling.
- Quantitative real-time PCR (qRT-PCR) to assess gene expression levels.
- Cellular assays including CCK-8, wound healing, and Transwell assays to evaluate cell proliferation, migration, and invasion.
- Western blot analysis for epithelial-mesenchymal transition (EMT) markers.
- Dual-luciferase reporter assays to confirm gene interactions.
Main Results:
- miR-133b was significantly downregulated in GC tissues, while COL1A1 expression was upregulated.
- Overexpression of miR-133b inhibited GC cell invasion, migration, and EMT, whereas silencing miR-133b had opposite effects.
- COL1A1 was identified as a direct target gene of miR-133b.
- COL1A1 was enriched in the TGF-β signaling pathway, and its activation promoted GC cell proliferation and migration.
- miR-133b overexpression suppressed the TGF-β pathway, and simultaneous overexpression of miR-133b and COL1A1 reversed the inhibitory effects.
Conclusions:
- miR-133b acts as a tumor suppressor in gastric cancer by inhibiting cell invasion and migration through the COL1A1/TGF-β axis.
- This study provides novel insights into the molecular pathogenesis of GC.
- The miR-133b/COL1A1/TGF-β pathway represents a potential therapeutic target for gastric cancer treatment.
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