Targeting Long Noncoding RNA UCA1 for Ovarian Cancer Therapy
Abstract
Lack of an effective targeted therapy contributes significantly to the high mortality rate in ovarian cancer. Our project is focused on evaluating the therapeutic potential of targeting UCA1, a long non-coding RNA, in ovarian cancer. To define the precise role of UCA1 in ovarian cancer pathobiology, we sought to investigate its interactomes in ovarian cancer cells. Towards this objective, we carried out RNA-pulldown assay coupled with liquid chromatography mass spectrometric analysis using cell extracts from the high grade serous ovarian cancer (HGSOC) cell line, OVCAR8. Our results Indicate that UCA1 primarily interacts with proteins involved in RNA processing and metabolism including proteins involved in the splicing of mRNAs. Interactome analysis using STRING and Cluster algorithms indicated the potential role of UCA1 in the activation of oncogenic alternative splicing (AS) switch to promote ovarian cancer growth and progression. Our results suggest that UCA1 changes the ratio of the two alternatively spliced variants of MENA (ENAH), namely an anti-invasive MENA11alpha and a pro-invasive MENAdelta11a/delta6 isoforms. Consistent with these findings, treatment of HGSOC cells with spliceosome inhibitors or silencing of MENA attenuates the invasive potential of ovarian cancer cells. Together, our results identify UCA1-regulated AS-switch as a critical mechanism underlying ovarian cancer progression and point to it as a potential therapeutic target in ovarian cancer for precision cancer medicine modalities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2022
- Accession Number
- AD1189986
Entities
People
- Danny N. Dhanasekaran
Organizations
- University of Oklahoma