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SIRT5 Directly Inhibits the PI3K/AKT Pathway in Prostate Cancer Cell Lines.


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.

SUBMITTER: Choi SY 

PROVIDER: S-EPMC8717960 | biostudies-literature | 2022 Jan-Feb

REPOSITORIES: biostudies-literature

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SIRT5 Directly Inhibits the PI3K/AKT Pathway in Prostate Cancer Cell Lines.

Choi So Young SY   Jeon Ju Mi JM   Na Ann Yae AY   Kwon Oh Kwang OK   Bang In Hyuk IH   Ha Yun-Sok YS   Bae Eun Ju EJ   Park Byung-Hyun BH   Lee Eun Hye EH   Kwon Tae Gyun TG   Lee Jun Nyung JN   Lee Sangkyu S  

Cancer genomics & proteomics 20220101 1


<h4>Background/aim</h4>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<sup>+</sup>-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  ...[more]

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