Peroxisomal β-oxidation enzyme, DECR2, regulates lipid metabolism and promotes treatment resistance in advanced prostate cancer.

"the rna sequencing data has been deposited with gene expression omnibus with accession number gse218282 v16d cells were treated with varying doses of tdz for 48 h in six-well plates.; data availability raw rna sequencing data are available through ncbi's gene expression omnibus under the accession number gse218282. differential expression analysis identified >8000 genes that were significantly (fdr < 0 05) differentially expressed in decr2 knockdown cells compared to control cells (supplementary data 1 ).; gene set enrichment analysis (gsea) revealed a strong enrichment for go-terms/pathways (msigdb) related to the cell cycle and dna replication and repair processes among downregulated genes in decr2 knockdown cells compared with control cells (supplementary data 1 ).; other metabolic processes such as carboxylic acid pathways branched-chain amino acid and isoprenoid metabolic processes were enriched among genes upregulated in decr2 knockdown cells (fig 3b ; supplementary fig 3a ; supplementary data 1 ).; edges represent overlap between gene sets and edge width represents the number of genes that overlap (see supplementary data 1 ) c bar chart of enriched gsea hallmark terms among downregulated genes in decr2 knockdown cells v16d and mr49f cell cycle distribution 96 h after ( d ) sirna-mediated decr2 knockdown and ( e ) tdz treatment.; all 3 cell lines displayed a strong and consistent accumulation of many cellular lipids (fig 4b ; supplementary fig 4c ; supplementary data 2 ) in particular the cholesteryl esters glycerides sphingolipids and several classes of (lyso)-phospholipids such as pc pe pi and lpe (fig 4b ; supplementary fig 4e ).; the opposite effect on lipid accumulation was observed in decr2-overexpressing (hdecr2) lncap cells whereby we observed a significant reduction in total lipid levels (fig 4d ; supplementary fig 4d ; supplementary data 2 ).; dot size is proportionate to statistical significance (see supplementary data 2 ) c quantitative abundance per saturation group in lncap v16d and mr49f cells d lipidomic analysis of decr2 overexpression (hdecr2) cells relative to control (hcontrol) e quantitative abundance f relative abundance per saturation group in decr2 overexpression cells g lipid ontology (lion) enrichment analysis of relative lipid abundance in sicontrol versus sidecr2 lncap v16d and mr49f prostate cancer cells. data availability raw rna sequencing data are available through ncbi's gene expression omnibus under the accession number gse218282"

"Competing interests The authors declare no competing interests."

"Funding Open Access funding enabled and organized by CAUL and its Member Institutions."