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USP43 promotes gemcitabine resistance by regulating cholesterol homeostasis through E2F1 stabilization in bladder cancer

GSE299182 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/06/18 Platform GPL24676
Summary
Gemcitabine (GEM) serves as a foundational therapy for bladder cancer (BLCA), but chemoresistance significantly limits its therapeutic efficacy. Elucidating the molecular mechanisms underlying this resistance is crucial for reversing GEM resistance. In this study, we revealed that the classical oncogene E2F1 is highly expressed in GEM-resistant cells and promotes chemoresistance. We further demonstrated that E2F1 induces GEM resistance by transcriptionally activating NSDHL, a key enzyme in cholesterol biosynthesis, thereby increasing cholesterol production. Additionally, we characterized USP43 as the deubiquitinase responsible for stabilizing E2F1, which plays an essential role in the GEM-induced upregulation of E2F1 expression. Collectively, our findings highlight the critical role of the USP43/E2F1/NSDHL axis in cholesterol-mediated GEM resistance in BLCA, providing novel insights and therapeutic targets for overcoming chemoresistance.
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Direct links to NCBI, no account and no request form: the whole study as GSE299182_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1273038 and SRA study SRP590379. Searching any of these in the dataset finder brings you back here.

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