Therapeutic potential and use of novel CRISPR technology for lncRNA knockdown in rhabdomyosarcoma
Mentor Name: Corinnr Linardic
Rhabdomyosarcoma (RMS) is a cancer related to the skeletal muscle lineage, and the most common soft tissue sarcoma of childhood. With the advent of next-gen sequencing, a variety of mutations in protein-coding genes have been found to participate in driving RMS tumorigenesis. This is important because some of these proteins may be useful in the future as biomarkers or therapeutic targets. However, up to one-quarter of RMS tumors have no such identified mutations. Recently we determined that long non-coding RNAs (long non-coding RNAs are RNA transcripts that are at least 200 nucleotides long but don't code for proteins) also support RMS tumorigenesis, and we have been learning how to manipulate these regulatory nucleic acids. Being able to achieve genetic and pharmacologic gain and loss of function would be a tremendous addition to the “molecular biology toolbox” of studying RMS. However, long noncoding RNAs often use different transcriptional machinery to control their expression. The research goal of this POST program project is to establish and test a new CRISPRi system that specifically targets long noncoding RNAs and see whether suppressing oncogenic long noncoding RNAs can be achieved in human RMS cell lines in vitro. The training goal is to provide a supportive, constructive summer research experience that will produce discrete, sound experimental results, but also engender enthusiasm and excitement for the future pursuit of childhood cancer research.
