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MRTF-A/SRF signaling suppresses invasion of oral squamous cell carcinoma
Dan Yang1, Dan Yang1, Yuqing He1
1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Background:
Serum response factor (SRF) and myocardial-associated transcription factor-A (MRTF-A) had different regulatory effects on the tumorigenesis and development in different cancers. However, the role of MRTF-A/SRF in oral squamous cell carcinoma (OSCC) remains to be determined.
Methods:
CCK-8 assay, cell scratch experiment, and transwell invasion assay were conducted to investigate the effects of MRTF-A/SRF on biological behavior of OSCC cells. The expression pattern and prognostic value of MRTF-A/SRF in OSCC were analyzed based on cBioPortal website and TCGA database. Protein-protein interaction network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to investigate related pathways. The effect of MRTF-A/SRF on epithelial-mesenchymal transformation (EMT) of OSCC cells was explored by western blot assay.
Results:
Overexpression of MRTF-A/SRF inhibited the proliferation, migration, and invasion of OSCC cells in vitro. High expression of SRF was related to better prognosis of OSCC patients on hard palate, alveolar ridge, and oral tongue. Besides, overexpression of MRTF-A/SRF inhibited the EMT of OSCC cells.
Conclusion:
SRF was closely related to the prognosis of OSCC. High expression of SRF and its co-activator MRTF-A inhibited proliferation, migration, and invasion of OSCC cells in vitro, possibly via EMT suppression.
Insights
Serum response factor (SRF) and its co-activator myocardial-associated transcription factor-A (MRTF-A) were found to inhibit oral squamous cell carcinoma (OSCC) progression. High SRF expression correlates with better OSCC patient prognosis, potentially by suppressing epithelial-mesenchymal transition (EMT).
Area of Science:
- Molecular Oncology
- Cancer Biology
- Oral Cancer Research
Background:
- Serum response factor (SRF) and myocardial-associated transcription factor-A (MRTF-A) exhibit varied roles in cancer development.
- The specific involvement of the MRTF-A/SRF axis in oral squamous cell carcinoma (OSCC) pathogenesis is not well understood.
Purpose of the Study:
- To investigate the functional role of MRTF-A/SRF in the biological behavior of OSCC.
- To determine the prognostic significance of MRTF-A/SRF in OSCC patients.
- To explore the impact of MRTF-A/SRF on epithelial-mesenchymal transition (EMT) in OSCC.
Main Methods:
- In vitro assays (CCK-8, scratch, Transwell) assessed OSCC cell proliferation, migration, and invasion.
- TCGA and cBioPortal databases analyzed MRTF-A/SRF expression patterns and prognostic value.
- Western blot examined the effect on EMT; pathway analyses identified related mechanisms.
Main Results:
- Overexpression of MRTF-A/SRF significantly inhibited OSCC cell proliferation, migration, and invasion in vitro.
- High SRF expression was associated with improved prognosis in OSCC patients across multiple oral subsites.
- MRTF-A/SRF overexpression suppressed EMT in OSCC cells.
Conclusions:
- SRF is a significant prognostic factor in OSCC.
- High expression of SRF and its co-activator MRTF-A suppresses OSCC cell growth and metastasis.
- The inhibitory effects of MRTF-A/SRF on OSCC progression may be mediated through the suppression of EMT.
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