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

ABSTRACT

Sunitinib is widely used as a first­line 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 glutaminyl­peptide 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, sunitinib­non­responsive 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, CCCTC­binding factor (CTCF) and phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinib­resistant RCC.