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Updated: May 20, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

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Hepatocellular carcinoma cells downregulate PGAM2 via SIRT2-mediated deacetylation modification to enhance aerobic

Zexuan Wang1,2, Yaoyu Guo1,2, Kefei Hu1,2

  • 1Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

NPJ Precision Oncology
|May 16, 2025
PubMed

Insights

Phosphoglycerate mutase 2 (PGAM2) acts as a tumor suppressor in liver cancer. Its deacetylation by SIRT2 destabilizes PGAM2, promoting cancer growth and sensitivity to sorafenib.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Phosphoglycerate mutase 2 (PGAM2) is a key glycolytic enzyme.
  • PGAM2 protein and acetylation levels are reduced in hepatocellular carcinoma (HCC).
  • The precise role of PGAM2 in HCC progression is not well understood.

Purpose of the Study:

  • To investigate the functional significance of PGAM2 in HCC progression.
  • To elucidate the post-translational regulation of PGAM2 in HCC.
  • To explore PGAM2's potential as a therapeutic target in HCC.

Main Methods:

  • Knockdown of PGAM2 in HCC cell lines and in vivo models.
  • Identification of PGAM2 deacetylation site (K100) and its regulator (SIRT2).
  • Analysis of PGAM2's effect on aerobic glycolysis, LDHA, and STAT3 signaling.
  • Assessment of HCC cell sensitivity to sorafenib upon PGAM2 knockdown.

Main Results:

  • PGAM2 functions as a tumor suppressor, inhibiting HCC cell proliferation and tumor growth.
  • SIRT2-mediated deacetylation at K100 destabilizes PGAM2, leading to its degradation.
  • PGAM2 suppresses aerobic glycolysis via an enzymatic activity-independent mechanism.
  • PGAM2 knockdown upregulates LDHA expression through STAT3 activation.
  • PGAM2 knockdown enhances HCC cell sensitivity to sorafenib.

Conclusions:

  • PGAM2 exhibits a tumor-suppressive role in HCC progression.
  • SIRT2-mediated deacetylation is a key regulatory mechanism for PGAM2 stability.
  • PGAM2 influences HCC progression through modulation of glycolysis and STAT3 signaling.
  • PGAM2 and its regulatory pathway represent potential biomarkers and therapeutic targets for HCC.

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