Characterization of drug-induced splicing complexity in prostate cancer cell line using long read technology

Pac Symp Biocomput. 2018:23:8-19.

Abstract

We characterize the transcriptional splicing landscape of a prostate cancer cell line treated with a previously identified synergistic drug combination. We use a combination of third generation long-read RNA sequencing technology and short-read RNAseq to create a high-fidelity map of expressed isoforms and fusions to quantify splicing events triggered by treatment. We find strong evidence for drug-induced, coherent splicing changes which disrupt the function of oncogenic proteins, and detect novel transcripts arising from previously unreported fusion events.

MeSH terms

  • Alternative Splicing / drug effects*
  • Alternative Splicing / genetics*
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Line, Tumor
  • Computational Biology
  • Gene Expression Profiling
  • Gene Fusion / drug effects
  • Humans
  • Male
  • Mefloquine / administration & dosage
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics*
  • RNA Splicing / drug effects
  • RNA Splicing / genetics
  • RNA, Neoplasm / genetics
  • Sequence Analysis, RNA
  • Tamoxifen / administration & dosage

Substances

  • RNA, Neoplasm
  • Tamoxifen
  • Mefloquine