A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.
Roger AbounaderMyron GibertYing ZhangShekhar SahaPawel MarcinkiewiczCollin DubeKadie HudsonYunan SunSylwia BednarekBilhan ChagariAditya SarkarChristian Roig-LaboyNatalie NeaceKarim SaoudInitha SetiadyFarina HanifDavid SchiffPankaj KumarBenjamin KefasMarkus HafnerPublished in: Research square (2024)
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.
Keyphrases
- high grade
- low grade
- transcription factor
- poor prognosis
- cell proliferation
- long non coding rna
- endothelial cells
- high resolution
- stem cells
- gene expression
- dna damage
- binding protein
- current status
- long noncoding rna
- induced pluripotent stem cells
- atomic force microscopy
- adverse drug
- pluripotent stem cells
- free survival
- copy number