Cell metabolic profiling of colorectal cancer via 1H NMR

Clin Chim Acta. 2020 Nov:510:291-297. doi: 10.1016/j.cca.2020.07.039. Epub 2020 Jul 21.

Abstract

Background: Protein arginine methyltransferase 5 (PRMT5) belongs to a large family of protein arginine methyltransferases (PRMTs) that play essential role in gene transcription and regulate tumorigenesis. However, the role of PRMT5 in the regulation of cancer cell metabolism remains unclear.

Methods: Cell metabolomic analysis was performed on SW480 cells transfected with small interfering RNA (siRNA) specifically targeting PRMT5, followed by metabolomic pathway analysis.

Results: PRMT5 was overexpressed in colorectal cancer (CRC) tissues, and downregulation of PRMT5 suppressed CRC cell proliferation and the levels of PRMT5 and symmetric dimethylation of histone H3 (H3R8me2s). In addition, we found distinct differences in metabolite classification and function in PRMT5 knockdown SW480 cells compared to control SW480 cells. PRMT5 knockdown increased the levels of amino acids and carbohydrates, particularly related to the arginine metabolism such as glutamate, glutamine (Gln), proline, creatine, creatinine and phosphocreatine (PCr).

Conclusions: These findings revealed a key role for PRMT5 as a regulator of CRC cell metabolism to mediate arginine methylation in CRC cells.

Keywords: (1)H NMR; Colorectal cancer; Metabolomic profiling; PRMT5.

MeSH terms

  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Histones
  • Humans
  • Protein-Arginine N-Methyltransferases* / genetics
  • Protein-Arginine N-Methyltransferases* / metabolism
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Histones
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases