Abstract 4436: Ubiquitin-specific peptidase 24 decreases c-Myc expression to inhibit lung cancer formation

Lung cancer is a malignant lung tumor characterized by high incidence and motility. c-Myc is a transcription factor that plays an important role in oncogenic activation to influence cellular metabolism and proliferation. Ubiquitin-specific peptidase 24 (USP24) is one of the members of USPs family to regulate protein ubiquitination. However, it is lack of evidence to uncover the role of USP24 in cancer formation. In this study, we found that cell proliferation was significantly increased by USP24 knockdown in A549 cells as accompanied by the increase of c-Myc protein. In particular, the RNA level and protein stability of c-Myc were not affected by USP24 knockdown, suggesting that USP24 affects c-Myc through regulating the translational pathway. Furthermore, c-Myc participated in USP24-knocked down-induced proliferation, not migration. To further clarify the mechanism underlying the regulation of c-Myc by USP24, we investigated whether mTOR pathway is involved in c-Myc upregulation by USP24 knockdown. Herein rapamycin, the mTOR inhibitor, prevented c-Myc upregulation caused by USP24 knockdown, suggesting that USP24 affect the protein level of c-Myc by regulating mTOR-mediated translation. We found that the downstream signaling of mTOR is activated by USP24 knockdown, including S6K and RPS6 phosphorylation. In addition, USP24 knockdown induced the binding of activated PRS6 to 5′-UTR of c-Myc, indicating that USP24 regulates c-Myc through mTOR-mediated translation. However, USP24 did not affect the phosphorylation of mTOR at Ser-2448, implying that other phosphorylation residue(s) within mTOR might be regulated by USP24. Since mTOR pathway is critical for many cancers formation, understanding the role of USP24 in regulating mTOR pathway will contribute to develop strategies to fight lung cancer. Citation Format: Jan-Jong Hung, Wen-Chang Chang. Ubiquitin-specific peptidase 24 decreases c-Myc expression to inhibit lung cancer formation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4436.