Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction. Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells. Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.
|State||Published - Sep 11 2017|
Bibliographical noteFunding Information:
FunDing: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the NIH. (CA140474 and Clinical and Translational Science Award (CTSA) UL1TR001998); BD was supported by a RISE-DAAD fellowship.
© 2017, © The Author(s) 2017.
- Alternative splicing
- lymphocytes RNA
- splicing inhibition
ASJC Scopus subject areas
- Molecular Medicine
- Biochemistry, medical