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• W4377029312 abstract "<b>Abstract ID 23137</b> <b>Poster Board 48</b> <b>PURPOSE:</b> The association between clinical outcomes of prostate cancer (PCa) progression and lipid remodeling is not well understood. Although it is known that increases in select circulating lipids correlate to decreased patient survival, the mechanisms mediating alterations in these lipids are not fully explained. We recently reported a correlation between the levels of phosphatidic acid (PA) and diacylglycerol (DAG) in cells representing castration-resistant prostate cancer (CRPC). We further showed correlations between PA and DAG levels with a decreased expression of a phosphatidic acid phosphatase, specifically lipin-1[MCF1] . However, the ability of lipin-1 to mediate the PCa lipidomic profile remains unknown. <b>HYPOTHESIS:</b> We hypothesized that the expression of lipin-1 mediates PA and DAG levels in CRPC cells and controls the overall lipidomic profile. We further hypothesized that the lipidomic profile of the <i>LPIN1</i> knockdown CRPC cells will correlate to RNA alterations. <b>METHODS:</b><i>LPIN1</i> silencing was established using shRNA lentiviral particles and validated with immunoblot analysis. The effect of <i>LPIN1</i> silencing on lipin-2 and lipin-3 expression was also analyzed. The cBioPortal for Cancer Genomics online database (https://www.cbioportal.org/) was used to analyze the expression of <i>LPIN1</i>, <i>LPIN2</i> and <i>LPIN3</i> in human prostate carcinoma patients. Gleason Scores were used to stratify patients into two cohorts (6-7 and 8-10), and changes in <i>LPIN1</i>, <i>LPIN2</i> and <i>LPIN3</i> mRNA expression were compared. Lipids were isolated using the Bligh-Dyer extraction method from control shRNA and <i>LPIN1</i> knockdown PC-3 cell lines. Lipids were analyzed using a targeted-based quantitative HPLC-ESI-Orbitrap-MS approach. RNA alterations between control shRNA and <i>LPIN1</i> knockdown PC-3 cells was analyzed by Illumina NextSeq sequencing. <b>RESULTS:</b> Our data showed effective <i>LPIN1</i> knockdown in PC-3 cells, and the silencing of <i>LPIN1</i> increased the expression of lipin-2, but not lipin-3. Analysis of mRNA expression of <i>LPIN1</i>, <i>LPIN2</i> and <i>LPIN3</i> in PCa patients from two different clinical populations indicated that patients with higher Gleason scores (8-10) had significantly increased <i>LPIN3</i> mRNA expression than patients with lower Gleason scores (6-7). There was no correlation between Gleason Score and <i>LPIN1</i> and <i>LPIN2</i> mRNA expression. <b>CONCLUSIONS:</b> These data suggest that <i>LPIN1</i> mediates the overall lipidomic profile of CRPC cells and <i>LPIN1</i> silencing is compensated in these cells by increased lipin-2 expression. Higher <i>LPIN3</i> expression in patients with a higher Gleason score suggest that <i>LPIN3</i> may be used as a potential prognostic biomarker for advanced PCa. <b>Support/Funding Information:</b> Department of Defense Prostate Cancer Research Program Idea Development Award (PC150431 GRANT11996600)" @default.
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• W4377029312 date "2023-05-18" @default.
• W4377029312 modified "2023-09-29" @default.
• W4377029312 title "Lipin-1 Silencing Alters the Phospholipid Profiles of Castration-Resistant Prostate Cancer Cells" @default.
• W4377029312 doi "https://doi.org/10.1124/jpet.122.231370" @default.
• W4377029312 hasPublicationYear "2023" @default.
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