Targeting Long Noncoding RNA UCA1 for Ovarian Cancer Therapy
Abstract
High mortality rate in ovarian cancer is primarily due to lack of an effective targeted therapy. Our project is focused on defining the mechanistic role of UCA1, along non-coding RNA, in ovarian cancer pathobiology and evaluating the therapeutic potential of targeting UCA1 for therapy ovarian cancer. Results from previous research period have identified the determinant role of UCA1 in orchestrating ovarian cancer epigenome. In the current research period, we further probed this avenue of research to identify any novel druggable targets in UCA1-regulated epigenome. We report here that the silencing of UCA1 relieves the repressing effect of UCA1 on tumor suppressor genes such as TP53BP1, BRCA2, and NEFH. Reduced expression of these tumor-suppressor genes are associated with resistance to cisplatin and PARP-inhibitors. Thus, our results point to the therapeutic potential of targeting UCA1 for overcoming therapy resistance in ovarian cancer. Next, using chromatin isolation by RNA purification (ChIRP) analysis, we have identified the potential epigenetic role of UCA1 in driving ovarian cancer cells towards oncogenic cellular differentiation, metabolic reprogramming, and cellular migration. Further bioinformatic analyses of the ChIRP dataset, coupled with experimental validations, are anticipated to identify the critical genes in cancer epigenome that can be targeted for therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1164057
Entities
People
- Danny N. Dhanasekaran
Organizations
- University of Oklahoma