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Published on: May 10, 2021
Reciprocal expression of Slug and Snail in human oral cancer cells
Ryosuke Nakamura1, Hiroki Ishii2, Kaori Endo2
1Center for Medical Education and Sciences, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Abstract:
Snail, also called Snai1, is a key regulator of EMT. Snail plays crucial roles in cancer progression, including resistance to anti-tumor drugs and invasion by various cancer cells. Slug, also known as Snai2, is also involved in the aggravation of certain tumors. In this study, we examined the roles of Slug in human oral squamous cell carcinoma (OSCC) cells. Slug is highly expressed in these cells, and Slug siRNA effectively represses anti-tumor drug resistance and invasive properties. In addition, transforming growth factor (TGF)-β upregulates the expression of Snail and Slug and promotes resistance to anti-tumor drugs in OSCC cells. Surprisingly, Slug siRNA appears to upregulate Snail expression considerably in OSCC cells. Snail siRNA also appears to upregulate Slug expression. Thus, either Slug or Snail siRNA alone partially mitigates malignant phenotypes in the presence of TGF-β, whereas both Slug and Snail siRNAs together dramatically suppress them. Therefore, Slug and Snail in tandem, but not alone, are potential therapeutic targets for nucleic acid medicines to treat oral cancer.
Insights
Snail (Snai1) and Slug (Snai2) proteins drive oral cancer progression. Targeting both Snail and Slug with nucleic acid medicines shows promise for treating oral squamous cell carcinoma (OSCC).
Area of Science:
- Molecular Biology
- Cancer Research
- Oncology
Background:
- Snail (Snai1) and Slug (Snai2) are key regulators of epithelial-mesenchymal transition (EMT).
- These proteins are implicated in cancer progression, drug resistance, and invasion.
- Their specific roles in oral squamous cell carcinoma (OSCC) require further elucidation.
Purpose of the Study:
- To investigate the role of Slug (Snai2) in human oral squamous cell carcinoma (OSCC) cells.
- To determine the combined effects of Snail (Snai1) and Slug (Snai2) in OSCC.
- To explore the potential of targeting Snail and Slug for oral cancer therapy.
Main Methods:
- Utilized small interfering RNA (siRNA) to knockdown Slug and Snail expression in OSCC cells.
- Assessed the impact of siRNA on anti-tumor drug resistance and invasive properties.
- Investigated the effects of transforming growth factor (TGF)-β on Snail and Slug expression.
Main Results:
- Slug is highly expressed in OSCC cells, and its knockdown reduces drug resistance and invasion.
- TGF-β upregulates both Snail and Slug, enhancing drug resistance in OSCC.
- Knockdown of either Snail or Slug individually partially mitigates malignant phenotypes; combined knockdown dramatically suppresses them.
Conclusions:
- Slug and Snail act in tandem to promote malignant phenotypes in oral cancer.
- Targeting both Slug and Snail simultaneously is a promising therapeutic strategy for oral cancer.
- Nucleic acid medicines targeting Slug and Snail represent a potential treatment for oral cancer.
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