QPCT regulation by CTCF leads to sunitinib resistance in renal cell carcinoma by promoting angiogenesis

Int J Oncol. 2021 Jul;59(1):48. doi: 10.3892/ijo.2021.5228. Epub 2021 May 26.

Abstract

Sunitinib is widely used as a first‑line treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminyl‑peptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinib‑non‑responsive and ‑responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC. The upstream and downstream regulatory mechanisms of QPCT were also evaluated. On the whole, the data from the present study suggest that QPCT, CCCTC‑binding factor (CTCF) and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinib‑resistant RCC.

Keywords: 5‑bisphosphate 3‑kinase catalytic subunit alpha; CCCTC‑binding factor; glutaminyl‑peptide cyclotransferase; phosphatidylinositol‑4; sunitinib.

MeSH terms

  • A549 Cells
  • Aminoacyltransferases / metabolism*
  • Animals
  • CCCTC-Binding Factor / metabolism*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Class I Phosphatidylinositol 3-Kinases / metabolism*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Mice
  • Sunitinib / pharmacology*
  • Sunitinib / therapeutic use
  • Up-Regulation

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Aminoacyltransferases
  • glutaminyl-peptide cyclotransferase
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Sunitinib

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant nos. 82002700 and 82072836), Postdoctoral Science Foundation of China (grant nos. 2020M673678), and Postdoctoral Science Foundation of Jiangsu Province (grant no. 2020Z363).