Abstract

Using Non-Coding RNAs to Identify Cancer Cell Vulnerabilities

Alexander Pertsemlidis, Associate Professor, Dept. of Pediatrics, Cellular & Structural Biology, The University of Texas Health Science Center at San Antonio

We study non­coding RNAs (ncRNAs) and when, how, and why they regulate cancer cell viability and drug response. Candidate ncRNAs are identified through high-throughput screening and expression profiling. Regulatory interactions are predicted in silico and validated using qRT-PCR, protein quantification, and luciferase reporter assays. Cancer cell response to perturbations is assessed through flow cytometric analysis of cell cycle phase distribution, colony formation and caspase activation assays, and validated in mouse xenograft models. We have identified ncRNAs that selectively kill cancer cells or lead to their terminal differentiation and ncRNAs that selectively enhance cancer cell response to microtubule-targeting agents, revealing new vulnerabilities of cancer cells mediated by complex regulatory relationships between several classes of coding and non-coding RNAs. These ncRNAs have intrinsic value as biomarkers and therapeutic agents and the vulnerabilities that they uncover can be targeted with pathway-specific perturbations, both improving our understanding of cancer pathogenesis and drug response and adding broadly to our therapeutic armamentarium.