Spermidine synthase regulates extracellular vesicle secretion in castration resistant prostate cancer.
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ABSTRACT:
PROVIDER: PRJNA600204 | ENA |
REPOSITORIES: ENA
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Project description:Extracellular vesciles (EVs) have an important role in the tumor progression. However, the precise regulatrory mechanisms of EV secretion has not been clarified yet. We performed quantitive high-throughput screening to eluciade the key miRNAs for EV biogenesis in castration resistant prostate cancer (CRPC) using 22RV1 cells, and miR-1908 was selected as the miRNA regulating EV biogenesis in CRPC. To identify the genes that could be targeted by miR-1908, we performed mRNA micorarray analysis in 22RV1 after transfected of miR-1908 mimic or control miRNA.
2020-06-21 | GSE143350 | GEO
Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle weakness, seriously affects the life quality of patients. However, the underlying mechanism is not well defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) protein through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM package into EVs from primary tumor. Circulating SRM proteins enhance spermidine accumulation in skeletal muscle and type I collagen fibers biosynthesis in an eIF5A-dependent manner. Deposition of randomly aligned collogen fibers induced by SRM+ EVs results in skeletal muscle fibrosis and weakness, as well as bone matrix loss. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.
2025-04-03 | GSE285652 | GEO
Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM packaging into EVs from primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.
2025-04-03 | GSE263507 | GEO
Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM packaging into EVs from primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.
2025-04-03 | GSE263506 | GEO
Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM packaging into EVs from primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.
2025-04-03 | GSE263508 | GEO
Project description:Radiotherapy (RT) reduces the risk of cancer recurrence and death, while accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles (sEVs) to trigger skeletal muscle weakness upon RT. Mechanistically, RT-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of SRM protein, facilitating SRM packaging into EVs from primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon RT, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of RT-mediated muscle weakness when combined with losartan treatment.
2025-04-03 | GSE263505 | GEO
Project description:Arachidonic acid triggers spermidine synthase secretion from primary tumor to induce skeletal muscle weakness upon irradiation
| PRJNA1205374 | ENA
Project description:Two complementary experiments were performed to evaluate whether N8-propargyl spermidine is a substrate of deoxyhypusine synthase in cells. HEK293 and mouse embryonic fibroblast (MEF) cells were incubated with either N8-propargyl spermidine or spermidine, lysed, and subjected to CuAAC ligation with azido-PEG3-biotin. In the MEF experiment, biotinylated proteins were enriched on NeutrAvidin agarose resin, digested on-bead with trypsin, and, following TMT labeling and LC-MS/MS analysis, the data were processed in MaxQuant and analyzed for intensity enrichment in samples derived from cells treated with N8-propargyl spermidine versus spermidine. In the HEK293 experiment, proteins were digested with trypsin, biotinylated peptides were enriched on NeutrAvidin agarose resin, and after LC-MS/MS analysis and MaxQuant processing, the peptides were examined for the presence of N8-propargyl spermidine thio-triazole adducts on cysteine residues.
2026-03-13 | PXD071477 | Pride
Project description:eIF5A is a well-established protein substrate of deoxyhypusine synthase (DHS), which also requires spermidine as a small-molecule substrate. At the end of 2024, a publication claimed that RIPK1 is an additional DHS substrate and that N8-propargyl spermidine can also serve as a DHS substrate. To evaluate these claims, eIF5A and RIPK1 were subjected to in vitro hypusination in the presence of DHS, deoxyhypusine hydroxylase (DOHH; the enzyme that hydroxylates the deoxyhypusine residue generated by DHS), and either N8-propargyl spermidine or spermidine. For reactions containing N8-propargyl spermidine, the samples were split: one portion was directly digested with trypsin, whereas the other was subjected to CuAAC ligation with azido-PEG3-biotin prior to tryptic digestion. Following LC-MS/MS analysis and MaxQuant processing, the data were searched for peptides bearing hypusine, deoxyhypusine, and their N-propargylated analogs. In samples that underwent CuAAC ligation, additional searches were performed for PEG3-biotin-triazole-modified N8-propargyl-spermidine-derived hypusine and deoxyhypusine, as well as for cysteine-N8-propargyl spermidine thio-triazole adducts.
2026-03-13 | PXD071577 | Pride
Project description:Cancer cell-secreted spermidine synthase induces skeletal muscle fibrosis upon radiotherapy (Xenograft tumor)
| PRJNA1097659 | ENA