Targeting Satellite Repeat RNAs in High-Grade Serous Ovarian Cancer
Abstract
There is a critical need for novel therapeutic strategies in HGSOC, specifically for platinum-resistant disease. Recent work from our lab and others has discovered aberrant expression of repeat non-coding RNAs across many cancers, and these repeat RNAs have active reverse transcription (RT) and expansion in cancer genomes, are recognized by pathogen recognition receptors and can trigger cancer cell death and alterations in the immune microenvironment. Thus, the goals of this project to 1) define the spectrum of repeat RNAs expressed across epithelial ovarian cancers and link these to immune characteristics of the tumor and response to therapies and 2) target repeat RNA reverse transcription as a potential therapeutic strategy in HGSOC. To date, Total RNASeq was performed on 32 patient-derived ovarian cancer cell lines, 11HGSOC PDX, 11 additional ovarian cancer cell lines, revealing abundant repeat RNA expression from all three major subclasses. Comparison of repeatome data from HGSOC models with previously generated RNA-seq data from colorectal cancer and pancreatic ductal adenocarcinoma models shows that repeat RNA profiles are unique across epithelial cancers. In HGSOC models, we find SAT and HERV repeats display the most variable expression. In particular, HSATII, a cancer specific satellite, is strongly expressed in HGSOC and displays highly variable expression across different models. Preliminary data targeting HSATII RNA levels shows cytotoxicity in some HGSOC cell lines, and combinatorial therapies are currently being investigated in vitro and in vivo using xenograft models.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1115926
Entities
People
- Rebecca L. Porter
Organizations
- Massachusetts General Hospital