Abstract 3747: Transcribed ultra-conserved regions (TUCRs): A first computational and molecular characterization of an understudied class of molecules in gliomas

Abstract

Abstract Gliomas are the most common malignant primary brain tumors. Particularly, glioblastoma (GBM) is the most common and deadliest malignant brain tumor. Most glioma research has focused on protein-coding genes and much less on the non-coding transcripts that make up 98% of cellular RNA. Transcribed Ultra-Conserved Regions (TUCRs) represent an understudied class of molecules that are found highly conserved across multiple species, including 100% conservation in mouse and rat genomes. These 481 transcripts are highly resistant to variation and are commonly deregulated in cancer, which suggests regulatory and functional importance when considered along with their high degree of conservation. We performed the first-ever characterization of TUCRs in gliomas in silico. Using an elaborate workflow, we annotated and identified TUCRs that are deregulated in GBM and low-grade glioma (LGG), associated with patient outcomes, and predicted their function in glioma initiation and progression. Most TUCRs were long non-coding RNAs. Of these, we investigated the most highly upregulated intergenic TUCR, uc.110, in vitro and in vivo in glioma cell lines. Knockdown of uc.110 expression via siRNA resulted in reduced glioma cell accumulation, viability, and invasion in vitro while reducing tumor volume and increasing overall survival in vivo. Concurrent lentiviral overexpression of uc.110 partially rescued wild-type expression, accumulation, viability, and invasion in vitro. Therefore, it is likely that this TUCR is functioning as an oncogene within the context of GBM. Our study represents the first comprehensive characterization of TUCRs in gliomas and can serve as a foundation and framework for similar studies in gliomas and other cancers. Citation Format: Myron K. Gibert, Bilhan Chagari, Christian Roig-Laboy, Aditya Sarkar, Roger Abounader. Transcribed ultra-conserved regions (TUCRs): A first computational and molecular characterization of an understudied class of molecules in gliomas. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3747.