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Published on: June 9, 2023
Knockdown of REV7 Inhibits Breast Cancer Cell Migration and Invasion
Liu Feng1, Wang Wei, Zhang Heng
1Medical College, Qingdao University, Qingdao, China.
Abstract:
REV7 (also known as MAD2L2) is a multifunctional protein involved in DNA damage tolerance, cell cycle regulation, gene expression, and carcinogenesis. Although its expression is reportedly associated with poor prognosis in several kinds of human cancers, the significance of REV7 expression in breast malignancies is unclear. In this study, REV7 was found to be increased in breast cancer. We found that knockdown of REV7 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Meanwhile, overexpression of REV7 promoted the migration, invasion, and EMT of breast cancer cells. As shown by Western blot, knockdown of REV7 can promote TGF-β1 expression. Western blot analysis indicated that TGF-β1 may play a role as a downstream factor of REV7. Moreover, interference of TGF-β1 can also inhibit the cell's ability for migration, invasion, and EMT, as well as in a cell line whose REV7 is overexpressed. Taken together, these results contributed to a recognition of the oncogene functions of REV7 in breast cancer cells and provided a novel direction to treat breast cancer.
Insights
REV7 protein promotes breast cancer progression by increasing cell migration, invasion, and epithelial-mesenchymal transition (EMT). Inhibiting REV7 or its downstream factor TGF-β1 offers a potential therapeutic strategy for breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- REV7 (MAD2L2) is a multifunctional protein implicated in DNA damage, cell cycle, and carcinogenesis.
- REV7 expression correlates with poor prognosis in various cancers, but its role in breast cancer remains unclear.
Purpose of the Study:
- To investigate the role and significance of REV7 expression in breast cancer.
- To elucidate the underlying molecular mechanisms of REV7 in breast cancer progression.
Main Methods:
- Western blot analysis to assess protein expression levels.
- Gene knockdown and overexpression techniques in breast cancer cell lines.
- Assessment of cell migration, invasion, and epithelial-mesenchymal transition (EMT) assays.
Main Results:
- REV7 expression is elevated in breast cancer tissues.
- REV7 knockdown inhibits breast cancer cell migration, invasion, and EMT.
- REV7 overexpression promotes these aggressive phenotypes.
- REV7 influences TGF-β1 expression, a key downstream mediator of these processes.
Conclusions:
- REV7 functions as an oncogene in breast cancer.
- Targeting REV7 or TGF-β1 presents a novel therapeutic avenue for breast cancer treatment.
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