STYX Interacts with FBXW7 to Promote AML Proliferation via Inhibiting the Ubiquitination of CCNE1.

Acute myeloid leukemia (AML) is a challenging hematologic malignancy with a poor prognosis. STYX, a catalytically inactive phosphatase, is overexpressed in various cancers and has been shown to promote cellular proliferation. However, its clinical relevance and impact on AML cell behavior remain poorly understood. This study investigates the role of STYX in AML and elucidates its underlying molecular mechanisms. Peripheral blood samples were collected from 50 patients with AML and 25 healthy controls, and the expression of STYX and FBXW7 was analyzed using RT-qPCR and Western blot. THP-1 cells (AML cell line) were transfected with lentivirus vectors to overexpress STYX, FBXW7, or CCNE1. The effects of these proteins on THP-1 cell proliferation and apoptosis were assessed by RT-qPCR, Western blot, CCK-8, EdU, and TUNEL assays. Interactions between STYX and FBXW7, as well as FBXW7 and CCNE1, were confirmed via STRING analysis and endogenous co-immunoprecipitation (CO-IP). Furthermore, the ubiquitination level of CCNE1 was examined through immunoprecipitation (IP) and Western blot. Upregulated STYX mRNA and protein levels, along with downregulated FBXW7 mRNA and protein levels, were observed in peripheral blood samples from MLL-AF9 fusion gene-positive AML cases, with a negative correlation between STYX and FBXW7. Overexpression of STYX in AML cells increased cell viability, promoted proliferation, and inhibited apoptosis, thus accelerating AML progression. STYX overexpression also facilitated the interaction with FBXW7, downregulated FBXW7 expression, and impaired the ubiquitin-mediated degradation of CCNE1. FBXW7 overexpression reversed STYX-induced proliferation and apoptosis effects in AML cells, while CCNE1 overexpression counteracted the suppressive effects of FBXW7 on AML progression. STYX promotes AML proliferation by disrupting the ubiquitin degradation pathway of CCNE1 through its interaction with FBXW7, thereby accelerating disease progression. These findings indicate that targeting STYX may offer a promising therapeutic approach for AML.