Online Archive of University of Virginia Scholarship
A Comprehensive Analysis of Transcribed Ultra Conserved Regions Uncovers Important Regulatory Functions of Novel Non-coding Transcripts in Gliomas8 views
Author
Gibert Jr, Myron K, Microbiology - School of Medicine, University of Virginia
Advisors
Abounader, Roger, MD-MICR Microbiology, University of Virginia
Dudley, Andrew, MD-MICR Microbiology, University of Virginia
Zong, Hui, MD-MICR Microbiology, University of Virginia
Garcia-Blanco, Mariano, MD-MICR Microbiology, University of Virginia
Laurie, Gordon, MD-CELL Cell Biology, University of Virginia
Bouton, Amy, MD-MICR Microbiology, University of Virginia
Dutta, Anindya, MD-BIOC Biochem-Mole Genetics, University of Virginia
Bekiranov, Stefan, MD-BIOC Biochem-Mole Genetics, University of Virginia
Abstract
Transcribed Ultra-Conserved Regions (TUCRs) are a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. We then utilized functional assays to investigate the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR in gliomas, uc.110, identifying it as a new oncogene. uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. uc.110 activates the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.
National Institute of Neurological Disorders and Stroke (NINDS)
Schiff Foundation
National Cancer Center (NCI)
Related Links
github.com/abounaderlab/tucr_project
abounaderlab.org
mkgibertjr.com
Notes
This dissertation project was supported by NIH UO1 CA220841 (w/ diversity supplement awarded to Myron Gibert Jr), NINDS 1R21NS122136-01, NINDS RO1 NS122222, NCI Cancer Center Support Grant 5P30CA044579, and a Schiff Foundation grant (all to Roger Abounader).
Language
English
Rights
All rights reserved by the author (no additional license for public reuse)
Gibert Jr, Myron K. A Comprehensive Analysis of Transcribed Ultra Conserved Regions Uncovers Important Regulatory Functions of Novel Non-coding Transcripts in Gliomas. University of Virginia, Microbiology - School of Medicine, PHD (Doctor of Philosophy), 2025-12-05, https://doi.org/10.18130/7afj-pr35.
