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By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth
Zheng Li1, Xin Yu1, Yang Wang2
1Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Emerging evidence has shown that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. MiR-329 was previously reported to act as a tumor suppressor or oncogene in some types of cancer. However, its function in gastric cancer (GC) is unclear. Here, we found that miR-329 was down-regulated in GC compared with adjacent controls. Enforced expression of miR-329 inhibited proliferation, migration and invasion of gastric cancer cells in vitro. We identified T lymphoma invasion and metastasis 1 (TIAM1) gene as potential target of miR-329. MiR-329 levels inversely correlated with TIAM1 expression in GC. Importantly, TIAM1 rescued the miR-329-mediated inhibition of cell invasion and proliferation. Finally, reintroduction of miR-329 significantly inhibited tumor formation of GC in the xenograft mice. Our findings suggest that miR-329 is a tumor suppressor and potential therapeutic target of GC.
Insights
MicroRNA-329 (miR-329) acts as a tumor suppressor in gastric cancer (GC). Lower miR-329 levels promote GC cell proliferation and invasion, suggesting it is a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) is a prevalent malignancy globally.
- MicroRNAs (miRNAs) play critical roles in cancer development.
- The specific role of miR-329 in GC remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of miR-329 in gastric cancer.
- To identify potential molecular targets of miR-329 in GC.
- To evaluate miR-329 as a therapeutic target for GC.
Main Methods:
- Quantitative real-time PCR to measure miR-329 expression.
- In vitro assays (proliferation, migration, invasion) to assess miR-329 function.
- Western blotting and luciferase reporter assays to validate TIAM1 as a miR-329 target.
- Xenograft mouse models to evaluate tumor formation in vivo.
Main Results:
- miR-329 expression was significantly downregulated in GC tissues compared to adjacent normal tissues.
- Overexpression of miR-329 suppressed proliferation, migration, and invasion of GC cells in vitro.
- TIAM1 was identified as a direct target of miR-329, with inverse correlation in GC samples.
- Restoration of TIAM1 expression rescued the inhibitory effects of miR-329 on GC cell behaviors.
- In vivo studies demonstrated that miR-329 reintroduction inhibited GC tumor formation.
Conclusions:
- miR-329 functions as a tumor suppressor in gastric cancer.
- The miR-329/TIAM1 axis is crucial for regulating GC progression.
- miR-329 represents a promising therapeutic candidate for gastric cancer treatment.
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