CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification

Drug Resist Updat. 2023 Nov:71:101003. doi: 10.1016/j.drup.2023.101003. Epub 2023 Sep 2.

Abstract

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

Keywords: CcRCC; CircPTEN; DNMT1; METTL3; MTOR inhibitors; PTEN.

MeSH terms

  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Glucose Transporter Type 1
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • MTOR Inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Glucose Transporter Type 1
  • MTOR Inhibitors
  • Protein Kinase Inhibitors