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Aging-dependent dysregulation of EXOSC2 is maintained in cancer as a dependency

GSE233404 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/20 Platform GPL13112
Summary
Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of original aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated to geriatric diseases including premature aging and cancer progression. Here, we hypothesized that the aging-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging-traits (abnormal cell cycle & division and poor tissue differentiation). We used the embryonic stem cells as a unique tool to study EXOSC2 function as the aging-trait epigenetic memory determined in A-iPSC because these aging-traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of the EXOSC2 and controls the microtubule polymerization. We also validated these aging-traits as a dependency in a mouse model of colon carcinogenesis.
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Direct links to NCBI, no account and no request form: the whole study as GSE233404_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 PRJNA976202 and SRA study SRP439506. Searching any of these in the dataset finder brings you back here.

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