Ovarian cancers (OCs) are highly aggressive malignancies and cause more deaths than any other cancers of the female reproductive system. Survival rates for OCs are very poor: for advanced disease only ~30% of patients survive beyond 5 years. This is largely due to lack of effective drug targets for treatment of OCs. Therefore, novel approaches to identifying drug targets are urgently needed to reduce OC-related mortality.
So far, over 98% of research in OCs has only focused on protein-coding genes, and very little is known about the role of non-protein-coding RNAs (ncRNAs). We have recently identified a group of dysregulated ncRNAs, including overexpressed UCA1, HOTAIR and downregulated MEG3 in OCs. Large cohort data from The Cancer Genome Atlas show that the survival time of patients with high levels of UCA1 or HOTAIR is shorter. On the other hand, patients with high levels of MEG3 live longer. Together with other experimental data, UCA1 and HOTAIR are oncogene that might initiate or promote tumor growth, while MEG3 tends to be a tumor suppressor that inhibits tumor growth.
This proposal is utilizing the state-of-art technique RNA antisense purification to understand the mechanism of UCA1, HOTAIR and MEG3. The interacting partners of UCA1, HOTAIR or MEG3 will be identified and validated. Then their roles in ovarian cancer initiation and development will be functionally characterized. The studies will provide the functional mechanisms of UCA1, HOTAIR, and MEG3 in OC initiation and development and provide potential cancer cell vulnerabilities that could be exploited for novel OC treatments.
Xianzhi (Andrew) Lin, PhD, is a postdoctoral scientist in the Cedars-Sinai Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute. Dr. Lin received his bachelor’s diploma in Bioengineering from the Kunming University of Science and Technology in 2004, and a PhD in Microbiology from Institut Pasteur of Shanghai Chinese Academy of Sciences in 2012. Before joining Dr. Kate Lawrenson’s lab in November 2015, he worked as a postdoctoral researcher at the University of California, Los Angeles with Dr. Grace Xiao studying the molecular mechanisms of RNA regulation - including alternative splicing, RNA editing, and RNA degradation. Currently, his research focuses on elucidating the mechanism of long noncoding RNAs in the initiation and/or development of ovarian cancers.