ACTG1 promotes breast cancer aggressiveness and confers ribociclib resistance by deubiquitinating HSPA8 through UCHL3

In this study, we examined the biological significance of the actin gamma 1 (ACTG1)-UCHL3–HSPA8 axis in breast cancer. Through bioinformatic analysis, we recognized ACTG1 as a potential oncogenic factor in BRCA. By exploiting qRT-qPCR and Western blot analysis, we assessed the expression of ACTG1 and explored its impact on cellular proliferation, migration, and invasion. Our findings suggest that ACTG1 exerts its oncogenic effects in breast cancer cells through the EMT signaling pathway. By mining the BIOGRID database, we identified potential downstream regulatory genes; and co-immunoprecipitation assays confirmed protein interactions between ACTG1 and HSPA8. We also observed that ACTG1 promoted breast cancer cell proliferation, invasion, and migration via its interaction with HSPA8. Importantly, our study elucidated the facilitation by UCHL3 of HSPA8 deubiquitination by ACTG1. In conclusion, our study revealed a key role played by the ACTG1–UCHL3–HSPA8 axis in driving breast cancer progression as well as the role of ribociclib resistance. Our findings provide compelling evidence for the therapeutic potential of targeting this axis in breast cancer treatment strategies.