Targeting Long Noncoding RNA UCA1 for Ovarian Cancer Therapy
Abstract
Ovarian cancer's high mortality rate is largely due to the absence of effective targeted therapies. In addressing this, our project centered on the therapeutic potential of targeting UCA1, a long non-coding RNA. Our comprehensive research included gene amplification analysis, qRT-PCR, RNA-pulldown, mass spectrometric analysis, and in vivo xenograft models. We identified a two-fold mechanism of UCA1upregulation: gene amplification and activation by growth factors like Lysophosphatidic Acid (LPA). Notably, we discovered that multiple LPA-receptor sub-types stimulate UCA1 expression, with their collective silencing markedly reducing UCA1 levels. Additionally, UCA1functions as a competing endogenous RNA (ceRNA), inhibiting let-7 miRNAs, which in turn upregulates oncogenes such as c-Myc and Ras. In vivo studies confirmed that UCA1 silencing increases let-7 miRNAs, underscoring its significant role in ovarian cancer progression. Importantly, UCA1 interacts with spliceosome proteins, influencing the alternative splicing of key genes involved in cancer cell invasion, including MENA in addition to interacting with PRC family of protein to suppress the expression of tumor suppressors. Our findings not only deepen the understanding of UCA1s role in ovarian cancer but also spotlight it as a promising target for innovative therapeutic approaches, contributing significantly to the field of precision medicine in oncology.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2023
- Accession Number
- AD1229818
Entities
People
- Danny N. Dhanasekaran
Organizations
- University of Oklahoma Health Sciences Center