RNF6 promotes colorectal cancer invasion and migration via the Wnt/ ll-catenin pathway by inhibiting GSK3ll activity

Background: The purpose of this study was to explore the molecular mechanism underlying the interaction between ring finger protein 6 (RNF6) and glycogen synthase kinase 3ll (GSK3ll) in colorectal cancer (CRC). Methods: In this study, cell models of overexpressed or silenced RNF6 were established by liposome transfection, and IM-12 was used as the inhibitor of GSK3ll. Real-time quantitative PCR and western blots were used to detect the expression of RNF6, p-GSK3ll, GSK3ll, and ll-catenin, and MTT assays were used to quantify cell proliferation. The tumorigenicity of cells was observed by plate clonal formation assay; the invasiveness of cells was examined in Transwell Boyden chambers, and the migratory capacity of cells was tested by scratch wound assays. The rat CRC model was induced by AOM/DSS, in which we verified activity in the Wnt/ll-catenin pathway by examining GSK3ll phosphorylation. Results: RNF6 was upregulated in CRC samples and cell lines. Silencing or overexpressing RNF6 in colorectal cancer cells inhibited or promoted, respectively, the proliferation, tumorigenicity, invasion and migration of CRC cells, as well as expression of p-GSK3ll, GSK3ll and ll-catenin. IM-12 reversed the Wnt/ll-catenin-activated state change induced by RNF6 silencing and the inhibition of cell proliferation, tumorigenicity, invasion and migration. The same results were observed in vivo in the rat CRC model. Conclusions: Overexpression of RNF6 in CRC increased the GSK3ll phosphorylation level, which led to activation of the Wnt/ll-catenin pathway and promoted the invasion and migration of CRC cells, suggesting that RNF6 may be a novel target for the treatment of CRC.

Automated summary

Overall, RNF6 was found to be upregulated in CRC samples and cell lines. Silencing or overexpressing RNF6 in colorectal cancer cells had significant impacts on cell proliferation, tumorigenicity, invasion, and migration, as well as the expression of p-GSK3ll, GSK3ll, and ll-catenin. The inhibitor IM-12 was able to reverse the effects induced by RNF6 and showed promise in inhibiting the activation of the Wnt/ll-catenin pathway. These findings suggest that RNF6 may serve as a potential therapeutic target for CRC treatment.