The up-regulated expression level of deubiquitinating enzyme USP46 induces the apoptosis of A549 cells by TRAF6.

This study investigates the function of Ubiquitin-specific protease 46 (USP46), a deubiquitinase, in the context of lung cancer, particularly its role in regulating cell proliferation via the ubiquitination of TRAF6. In A549 lung cancer cells, analysis revealed a significant downregulation of USP46 expression, while TRAF6 levels were notably elevated. These findings were corroborated by Western blotting, which confirmed the altered expression patterns. To further assess the implications of these changes, several experimental assays, including the Cell Counting Kit-8, transwell migration assays, and flow cytometry, were conducted to evaluate cell viability and apoptosis rates. Co-immunoprecipitation experiments demonstrated a direct interaction between USP46 and TRAF6, implicating USP46 in the modulation of TRAF6 ubiquitination, a process that is fundamental to tumor physiology. The results indicated that decreased USP46 expression led to an increase in the levels of the anti-apoptotic protein Bcl-2, while there was a corresponding decrease in key pro-apoptotic proteins such as caspase-3, caspase-9, and Bax. Additionally, the study found elevated levels of phosphorylated AKT and mTOR, which suggest the activation of survival signaling pathways in the cancer cells. These findings collectively suggest that the up-regulated USP46 promotes apoptosis in lung cancer cells through the regulation of TRAF6. Therefore, targeting the USP46/TRAF6 signaling pathway presents a promising therapeutic strategy for lung cancer treatment, potentially offering new avenues for intervention in cancer progression and cell survival mechanisms.