A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas

TL;DR

This study explores non-coding RNA regions called TUCRs in brain tumors and finds one, uc.110, acts as an oncogene promoting tumor growth.

Contribution

The first comprehensive analysis of TUCRs in gliomas, identifying uc.110 as a novel oncogene with a specific mechanism of action.

Findings

Uc.110 is highly overexpressed in glioblastoma and low-grade gliomas.

Uc.110 promotes malignancy by activating the WNT pathway through MFRP upregulation.

Uc.110 sponges miR-544, a tumor suppressor microRNA.

Abstract

Transcribed Ultra-Conserved Regions (TUCRs) represent 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, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, 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 activated 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.

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