Inhibition of SDE2 promotes autophagy-dependent ferroptosis in multiple myeloma.

ABSTRACT:

Background

Multiple myeloma (MM) is an incurable plasma cell malignancy with high relapse rate. Recent studies have implicated dysregulated autophagy and ferroptosis in MM progression; however, the molecular links remain elusive. This study investigated the role of SDE2, a ubiquitin-like protein overexpressed in MM, in modulating autophagy-ferroptosis crosstalk via ATG5 degradation with the aim of identifying novel therapeutic targets.

Methods

Using bioinformatic analysis of TCGA data, we identified SDE2 as a prognostic marker in MM. Functional validation included Western blot, co-immunoprecipitation, and ubiquitination assays in MM cell lines (H929, RPMI8226, OPM-2, and KMS-11) and patient-derived samples. Transwell migration, soft agar colony formation, and flow cytometry

SUBMITTER: Xia L 

PROVIDER: S-EPMC12907901 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature