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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
The EMT-related transcription factor snail up-regulates FAPα in malignant melanoma cells
Yanmei Yi1, Zhaotong Wang2, Yanqin Sun3
1Department of Histology and Embryology, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.
Abstract:
FAPα is a cell surface serine protease, mainly expressed in tumor stromal fibroblasts in more than 90% of human epithelial carcinomas. Due to its almost no expression in normal tissues and its tumor-promoting effects, FAPα has been studied as a novel potential target for antitumor therapy. However, the regulation mechanism on FAPα expression is poorly understood. In this study, we found that overexpression of snail significantly increased the mRNA and protein expression levels of FAPα in malignant melanoma B16 and SK-MEL-28 cells. Overexpression of snail increased FAPα promoter activity remarkably. Snail could directly bind to FAPα promoter to regulate FAPα expression. Moreover, snail expression was positively correlated to FAPα expression in human cutaneous malignant melanoma. Furthermore, knockdown of FAPα markedly reduced snail-induced cell migration. Overall, our findings provide a novel regulation mechanism on FAPα expression and highlight the role of snail/FAPα axis as a novel target for melanoma treatment.
Insights
Fibroblast activation protein alpha (FAPα) expression in melanoma is increased by the snail protein. This snail/FAPα axis presents a new therapeutic target for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Fibroblast activation protein alpha (FAPα) is a serine protease highly expressed in tumor stroma, making it a potential cancer therapy target.
- Understanding FAPα regulation is crucial for developing effective antitumor strategies.
Purpose of the Study:
- To investigate the regulatory mechanism of FAPα expression.
- To explore the role of the snail protein in FAPα regulation and its impact on melanoma.
Main Methods:
- Overexpression and knockdown of snail and FAPα in melanoma cell lines (B16, SK-MEL-28).
- Analysis of FAPα mRNA and protein levels, promoter activity assays, and chromatin immunoprecipitation.
- Correlation analysis of snail and FAPα expression in human melanoma tissues.
- Cell migration assays.
Main Results:
- Snail overexpression significantly upregulated FAPα mRNA and protein levels in melanoma cells.
- Snail directly binds to the FAPα promoter, enhancing its activity.
- Snail expression positively correlates with FAPα expression in human cutaneous malignant melanoma.
- FAPα knockdown inhibited snail-induced melanoma cell migration.
Conclusions:
- Snail is a novel regulator of FAPα expression in melanoma.
- The snail/FAPα axis represents a promising therapeutic target for melanoma treatment.
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