RYBP contributes to improved prognosis in colorectal cancer via regulation of cell cycle, apoptosis and oxaliplatin sensitivity

Int J Oncol. 2023 Nov;63(5):120. doi: 10.3892/ijo.2023.5568. Epub 2023 Sep 1.

Abstract

Ring1 and YY‑1 binding protein (RYBP) is a member of the polycomb repressive complex 1 and serves as a transcriptional suppressor via epigenetic modification. RYBP has a tumour‑suppressive role in solid tumours, but its function in colorectal cancer (CRC) remains unknown. The present study evaluated the expression of RYBP using immunohistochemistry in 140 cases of primary CRC and 11 patient‑matched cases of liver metastases. Using CRC cell lines with different TP53 gene status such as HCT116 (TP53wt/wt), HCT116 (TP53‑/‑), SW48 and DLD‑1 cells, proliferation, cell cycle progression and apoptosis, as well as the effect of RYBP on oxaliplatin sensitivity, were assessed. Clinical data showed that low RYBP expression was significantly associated with risk of distant metastasis and recurrence, and patients with high RYBP expression demonstrated significantly better cancer‑specific and disease‑free survival. In vitro experiments revealed that RYBP suppressed cell proliferation by inducing cell cycle arrest and apoptosis in TP53 wild‑type cells. In addition, endogenous RYBP overexpression enhanced sensitivity to oxaliplatin. Therefore, RYBP may contribute to improved prognosis in CRC by regulating the cell cycle, apoptosis and oxaliplatin sensitivity via the p53‑mediated pathway.

Keywords: RYBP; apoptosis; cell cycle; chemo‑ resistance; tumour suppressor.

MeSH terms

  • Apoptosis*
  • Cell Cycle
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Humans
  • Oxaliplatin / pharmacology
  • Prognosis
  • Repressor Proteins

Substances

  • Oxaliplatin
  • RYBP protein, human
  • Repressor Proteins

Grants and funding

The present study was supported by the Japan Society for the Promotion of Science KAKENHI (grant no. JP22K08889).