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MiR-497 enhances metastasis of oral squamous cell carcinoma through SMAD7 suppression
Jun Hu1, Jun-Feng Xu2, Wei-Li Ge3
1Department of Prosthodontics, Hospital of Stomatology Affiliated to Zhejiang University Hangzhou 310006, China.
Abstract:
SMAD7 is a key inhibitor of transforming growth factor β (TGFβ) receptor signaling, which regulates the alteration of cancer cell invasiveness through epithelial-mesenchymal cell conversion. Since microRNAs (miRNAs) play a potential role in the tumorigenesis, cancer cell growth and metastases of oral squamous cell carcinoma (OSCC), determination of the involved miRNAs that may regulate SMAD7-mediated OSCC cell invasion appears to be one important question. Here, we found that the levels of miR-497 were significantly increased and the levels of SMAD7 were significantly decreased in OSCC specimens, compared to the paired adjacent non-tumor tissue. Moreover, miR-497 and SMAD7 inversely correlated in OSCC specimens. The 5-year survival of the patients with higher miR-497 levels in the resected OSCC was worse than those high miR-497 levels. Bioinformatics analyses showed that miR-497 targeted the 3'-UTR of SMAD7 mRNA to inhibit its translation, which was proved by luciferase reporter assay. Furthermore, miR-497 overexpression increased SMAD7-suppressed cell invasion, while miR-497 depletion decreased SMAD7-suppressed cell invasion in OSCC cells, in both a transwell cell invasion assay and a scratch would healing assay. Together, our data suggest that suppression of miR-497 in OSCC cells may promote cancer cell invasion via suppression of SMAD7, and highlight miR-497 as an intriguing therapeutic target to prevent OSCC metastases.
Insights
MicroRNA-497 (miR-497) levels increase while SMAD7 levels decrease in oral squamous cell carcinoma (OSCC), promoting cancer cell invasion. Suppressing miR-497 may inhibit OSCC metastasis by restoring SMAD7 levels.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Transforming growth factor β (TGFβ) signaling regulates epithelial-mesenchymal transition, impacting cancer cell invasiveness.
- MicroRNAs (miRNAs) are implicated in oral squamous cell carcinoma (OSCC) tumorigenesis and metastasis.
- SMAD7 acts as a key inhibitor of TGFβ receptor signaling.
Purpose of the Study:
- To investigate the role of miR-497 in regulating SMAD7-mediated OSCC cell invasion.
- To determine the correlation between miR-497 and SMAD7 levels in OSCC specimens.
- To explore the therapeutic potential of targeting miR-497 in OSCC metastasis.
Main Methods:
- Quantitative analysis of miR-497 and SMAD7 expression in OSCC tissues and adjacent non-tumor tissues.
- Bioinformatics analysis to predict miR-497 targets.
- Luciferase reporter assay to validate miR-497 targeting of SMAD7.
- In vitro cell invasion assays (Transwell and scratch wound healing) to assess the functional role of miR-497 and SMAD7.
Main Results:
- miR-497 levels were significantly elevated, and SMAD7 levels were significantly decreased in OSCC specimens compared to non-tumor tissues.
- A significant inverse correlation was observed between miR-497 and SMAD7 expression in OSCC.
- Higher miR-497 levels correlated with worse 5-year survival in OSCC patients.
- miR-497 directly targets and inhibits SMAD7 translation.
- Modulating miR-497 levels affected OSCC cell invasion, with overexpression promoting invasion and depletion inhibiting it.
Conclusions:
- miR-497 promotes OSCC cell invasion by suppressing SMAD7.
- The miR-497/SMAD7 axis represents a potential therapeutic target for preventing OSCC metastasis.
- Targeting miR-497 could offer a novel strategy for OSCC treatment.
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