Objective: Triple-negative breast cancer (TNBC) is a subtype with high invasiveness. Due to lacking specific and effective therapies, it is necessary to explore the mechanism of TNBC progression and search for new therapeutic targets.
Methods: Data from the GEPIA2 database was analyzed to explore RNF43 expression in each subtype of breast cancer. RNF43 expression in TNBC tissue and cell lines was determined by RT-qPCR. In vitro biological function analyses including MTT assay, colony formation assay, wound-healing assay and Transwell assay were conducted to explore the role of RNF43 in TNBC. In addition, the markers of epithelial-mesenchymal transition (EMT) were detected by western blot. The expression of β-Catenin and its downstream effectors were also detected.
Results: Data from the GEPIA2 database indicated that RNF43 expression was lower in tumor tissue compared to paired adjacent tissue in TNBC. In addition, RNF43 expression in TNBC was lower than in other subtypes of breast cancer. Consistently, down-regulation of RNF43 expression in TNBC tissue and cell lines was observed. Overexpressing RNF43 attenuated the proliferation and migration of TNBC cells. Depletion of RNF43 showed the opposite effect, confirming that RNF43 played an anti-oncogenic role in TNBC. In addition, RNF43 suppressed several markers of EMT. Furthermore, RNF43 restrained the expression of β-Catenin and its downstream effectors, implying RNF43 exerted the suppressive role in TNBC by inhibiting the β-Catenin pathway.
Conclusions: This study demonstrated that the RNF43-β-Catenin axis attenuated TNBC progression, which might provide novel therapeutic targets for TNBC.
Keywords: EMT; RNF43; Triple-negative breast cancer; β-Catenin.
© 2023 by the Association of Clinical Scientists, Inc.