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P5CS deacetylation mediated by SIRT2 facilitates tumor growth by enhancing mitochondrial respiration in hepatocellular carcinoma

  • 0Xinxiang Key Laboratory of Inflammation and Immunology, School of Medical Technology, Xinxiang Medical University, Xinxiang, Henan, 453003, China. xfgeng0922@163.com.
Oncogene +

|

May 27, 2025

|

May 27, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study reveals that SIRT2 activates proline synthesis enzyme P5CS in liver cancer (HCC). This activation boosts cancer cell energy production and growth, suggesting SIRT2 as a potential therapeutic target for HCC.

Area Of Science

  • Biochemistry
  • Molecular Biology
  • Oncology

Background

  • Cancer cells rely on enhanced mitochondrial metabolism for energy and biosynthesis.
  • The enzyme delta-1-pyrroline-5-carboxylate synthase (P5CS), crucial for proline synthesis, is upregulated in tumors.
  • Mechanisms regulating P5CS in hepatocellular carcinoma (HCC) are not well understood.

Purpose Of The Study

  • To investigate the role of P5CS and its regulatory mechanisms in HCC development.
  • To explore the relationship between P5CS expression and HCC patient prognosis.

Main Methods

  • Analysis of P5CS expression in HCC tissues.
  • Knockdown experiments to assess the impact of P5CS and SIRT2 on HCC cell behavior.
  • Co-immunoprecipitation and Western blotting to study SIRT2-P5CS interaction and P5CS deacetylation.
  • Measurement of mitochondrial respiration.

Main Results

  • P5CS is highly expressed in HCC and linked to poor prognosis.
  • P5CS knockdown inhibits HCC cell proliferation, migration, and invasion by reducing mitochondrial respiration.
  • SIRT2 interacts with and deacetylates P5CS at K311 and K347, activating its enzymatic activity.
  • SIRT2 knockdown also inhibits HCC cell proliferation, migration, and invasion.

Conclusions

  • SIRT2-mediated deacetylation of P5CS activates mitochondrial respiration, promoting HCC cell proliferation and tumorigenesis.
  • Targeting SIRT2-mediated P5CS deacetylation presents a potential therapeutic strategy for HCC.

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