So Young Choi1, Ju Mi Jeon1, Ann Yae Na1, Oh Kwang Kwon1, In Hyuk Bang2, Yun-Sok Ha3, Eun Ju Bae4, Byung-Hyun Park2, Eun Hye Lee5, Tae Gyun Kwon3, Jun Nyung Lee6, Sangkyu Lee7. 1. BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea. 2. Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonbuk, Republic of Korea. 3. Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 4. College of Pharmacy, Chonbuk National University, Jeonbuk, Republic of Korea. 5. Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea. 6. Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; ljnlover@gmail.com. 7. BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; sangkyu@knu.ac.kr ljnlover@gmail.com.
Abstract
BACKGROUND/AIM: Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men globally. Among patients who develop advanced PCa, 80% are affected by bone metastasis, with a sharp drop in survival rate. Despite efforts, the details of mechanisms of metastasis of PCa remain unclear. SIRT5, an NAD+-dependent deacylase, is hypothesized to be a crucial regulator of various cancers. The role of SIRT5 in cancer has not been extensively studied compared to other SIRTs. In this study, we showed significantly decreased levels of SIRT5 in PC-3M, a highly aggressive PC-3 cell variant. MATERIALS AND METHODS: We characterized the differentially expressed proteins between parental and SIRT5 KO PC-3 cells using quantitative proteomics analysis. RESULTS: A significant increase in expression of interleukin-1β (IL-1β) in SIRT5 KO cells was observed, and the PI3K/AKT/NF-ĸB signaling pathway was found significantly elevated in SIRT5 KO cells by the Gene Ontology annotation and KEGG pathway functional enrichment analysis. Moreover, we confirmed that SIRT5 can bind PI3K by immunoprecipitation analysis. CONCLUSION: This study is the first to demonstrate a relationship between SIRT5 and PCa metastasis, suggesting that SIRT5-mediated inhibition of the PI3K/AKT/NK-kB pathway is reduced for secondary metastasis from bone to other tissues.
BACKGROUND/AIM: Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men globally. Among patients who develop advanced PCa, 80% are affected by bone metastasis, with a sharp drop in survival rate. Despite efforts, the details of mechanisms of metastasis of PCa remain unclear. SIRT5, an NAD+-dependent deacylase, is hypothesized to be a crucial regulator of various cancers. The role of SIRT5 in cancer has not been extensively studied compared to other SIRTs. In this study, we showed significantly decreased levels of SIRT5 in PC-3M, a highly aggressive PC-3 cell variant. MATERIALS AND METHODS: We characterized the differentially expressed proteins between parental and SIRT5 KO PC-3 cells using quantitative proteomics analysis. RESULTS: A significant increase in expression of interleukin-1β (IL-1β) in SIRT5 KO cells was observed, and the PI3K/AKT/NF-ĸB signaling pathway was found significantly elevated in SIRT5 KO cells by the Gene Ontology annotation and KEGG pathway functional enrichment analysis. Moreover, we confirmed that SIRT5 can bind PI3K by immunoprecipitation analysis. CONCLUSION: This study is the first to demonstrate a relationship between SIRT5 and PCa metastasis, suggesting that SIRT5-mediated inhibition of the PI3K/AKT/NK-kB pathway is reduced for secondary metastasis from bone to other tissues.
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