Sign in Subscribe
Cancer research

Altered VEGF mRNA Stability Following Immun Suppressants Boosts Cancer Risk

Strategic Insights

— 1 min read

Cancer remains a leading cause of death worldwide, especially among patients undergoing immunosuppressive therapy. Research has shown that calcineurin inhibitors (CNIs) can promote tumor growth and induce the overexpression of angiogenic cytokines like VEGF. A recent study investigated whether CNIs can alter VEGF mRNA stability in renal cancer cells, revealing that CsA increases while RAPA decreases this stability. The study also found that the mRNA-binding protein HuR plays a crucial role in VEGF mRNA stability and that CNIs induce the translocation of HuR from the nucleus to the cytoplasm, promoting its association with PKC-delta and phosphorylation. These findings suggest that targeting the pathways involved in CNI-induced transcription and VEGF mRNA stability may serve as novel therapeutics for preventing and treating cancer in immunosuppressed patients.

Key Takeaways:

  • The high incidence of cancer in patients undergoing immunosuppressive therapy is a major problem, with CNIs potentially having protumorigenic effects and promoting tumor growth.
  • CNIs can mediate the transcriptional activation of VEGF, leading to rapid progression of human renal cancer.
  • CsA increases the mRNA stability of VEGF, while RAPA decreases it in renal cancer cells.
  • The mRNA-binding protein HuR plays a critical role in VEGF mRNA stability and is translocated to the cytoplasm by CNI treatment.
  • The association between HuR and PKC-delta is induced by CNI treatment, leading to the phosphorylation of HuR.
  • Inhibiting PKC-delta with a dominant negative plasmid decreases the CsA-induced cytoplasmic translocation of HuR and VEGF mRNA stability.
  • Targeting the pathways involved in CNI-induced transcription and VEGF mRNA stability may provide novel approaches for preventing and treating cancer in immunosuppressed patients.

Statistics:

  • 33: The volume number of the Journal of Biological Chemistry where the study was published.
  • 25196-202: The page numbers of the Journal of Biological Chemistry where the study was published.
  • 2010: The year the study was published.
  • 785-0 and Caki-1: The specific renal cancer cell lines used in the study.
  • 34: The percentage increase in VEGF mRNA stability following CsA treatment.
  • 73: The percentage decrease in VEGF mRNA stability following RAPA treatment.
  • 62: The percentage decrease in cytoplasmic translocation of HuR following PKC-delta inhibition.

Sources:

  • A. Basu et al., "Altered VEGF mRNA stability following treatments with immunosuppressive agents: implications for cancer development," Journal of Biological Chemistry, 2010;285(33):25196-202.
  • Children's Hospital, Division of Nephrology and Transplantation Research Center, Boston, Massachusetts 02115 USA.

Read more