AUTHOR=Širvinskas Dovydas , Steponaitis Giedrius , Stakaitis Rytis , Tamašauskas Arimantas , Vaitkienė Paulina , Skiriutė Daina 

TITLE=Antisense lncRNA CHROMR is linked to glioma patient survival

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1101953

DOI=10.3389/fmolb.2023.1101953

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> Natural non-coding antisense transcripts (ncNATs) are long non-coding RNAs (lncRNA) transcribed from the opposite strand of a separate protein coding or non-coding gene. As such, ncNATs can increase overlapping mRNA (and the coded protein) levels by stabilizing mRNA, absorbing inhibitory miRNAs and protecting the mRNA from degradation, or conversely decrease mRNA (or protein) levels by directing the mRNA towards degradation or inhibiting protein translation. Recently, growing numbers of ncNATs were shown to be dysregulated in cancerous cells, however, actual impact of ncNATs on cancer progression remains largely unknown. We therefore investigated gene expression levels of natural antisense lncRNA <italic>CHROMR</italic> (Cholesterol Induced Regulator of Metabolism RNA) and its sense protein coding gene <italic>PRKRA</italic> (Protein Activator of Interferon Induced Protein Kinase EIF2AK2) in gliomas. Next, we checked <italic>CHROMR</italic> effect on the survival of glioma patients.</p><p><bold>Methods:</bold> We performed RNA-seq on post-surgical tumor samples from 26 glioma patients, and normal brain tissue. Gene expression in TPM values were extracted for <italic>CHROMR</italic> and <italic>PRKRA</italic> genes. These data were validated using the TCGA and GTEx gene expression databases.</p><p><bold>Results:</bold> The gene expression level of ncNAT lncRNA <italic>CHROMR</italic> in glioma tissue was significantly higher compared to healthy brain tissue, while the expression of its sense counterpart protein coding <italic>PRKRA</italic> mRNA did not differ between glioma and healthy samples. Survival analysis showed lower survival rates in patients with low mRNA <italic>PRKRA</italic>/lncRNA <italic>CHROMR</italic> gene expression ratio compared to high ratio showing a link between lncRNA <italic>CHROMR</italic> and glioma patient survival prognosis.</p><p><bold>Conclusion:</bold> Here we show that elevated levels of lncRNA <italic>CHROMR</italic> (i.e., low ratio of mRNA <italic>PRKR</italic>A/lncRNA <italic>CHROMR</italic>) is associated with poor prognosis for glioma patients<italic>.</italic></p>