Phosphoglycerate mutase 1 knockdown inhibits prostate cancer cell growth, migration, and invasion

Asian J Androl. 2018 Mar-Apr;20(2):178-183. doi: 10.4103/aja.aja_57_17.

Abstract

Phosphoglycerate mutase 1 (PGAM1) is upregulated in many cancer types and involved in cell proliferation, migration, invasion, and apoptosis. However, the relationship between PGAM1 and prostate cancer is poorly understood. The present study investigated the changes in PGAM1 expression in prostate cancer tissues compared with normal prostate tissues and examined the cellular function of PGAM1 and its relationship with clinicopathological variables. Immunohistochemistry and Western blotting revealed that PGAM1 expression was upregulated in prostate cancer tissues and cell lines. PGAM1 expression was associated with Gleason score (P = 0.01) and T-stage (P = 0.009). Knockdown of PGAM1 by siRNA in PC-3 and 22Rv1 prostate cancer cell lines inhibited cell proliferation, migration, and invasion and enhanced cancer cell apoptosis. In a nude mouse xenograft model, PGAM1 knockdown markedly suppressed tumor growth. Deletion of PGAM1 resulted in decreased expression of Bcl-2, enhanced expression of Bax, caspases-3 and inhibition of MMP-2 and MMP-9 expression. Our results indicate that PGAM1 may play an important role in prostate cancer progression and aggressiveness, and that it might be a valuable marker of poor prognosis and a potential therapeutic target for prostate cancer.

Keywords: apoptosis; invasion; migration; phosphoglycerate mutase 1; proliferation; prostate cancer.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Gene Deletion
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • Neoplasm Transplantation
  • PC-3 Cells
  • Phosphoglycerate Mutase / genetics*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering
  • Transplantation, Heterologous
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • bcl-2-Associated X Protein
  • Caspase 3
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Phosphoglycerate Mutase
  • phosphoglycerate mutase 1, human