Expression and regulatory roles of lncRNAs in G-CIMP-low vs G-CIMP-high Glioma: an in-silico analysis

Indrani Datta, Houtan Noushmehr, Chaya Brodie, Laila M. Poisson

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5 Scopus citations

Abstract

Background: Clinically relevant glioma subtypes, such as the glioma-CpG island methylator phenotype (G-CIMP), have been defined by epigenetics. In this study, the role of long non-coding RNAs in association with the poor-prognosis G-CMIP-low phenotype and the good-prognosis G-CMIP-high phenotype was investigated. Functional associations of lncRNAs with mRNAs and miRNAs were examined to hypothesize influencing factors of the aggressive phenotype. Methods: RNA-seq data on 250 samples from TCGA’s Pan-Glioma study, quantified for lncRNA and mRNAs (GENCODE v28), were analyzed for differential expression between G-CIMP-low and G-CIMP-high phenotypes. Functional interpretation of the differential lncRNAs was performed by Ingenuity Pathway Analysis. Spearman rank order correlation estimates between lncRNA, miRNA, and mRNA nominated differential lncRNA with a likely miRNA sponge function. Results: We identified 4371 differentially expressed features (mRNA = 3705; lncRNA = 666; FDR ≤ 5%). From these, the protein-coding gene TP53 was identified as an upstream regulator of differential lncRNAs PANDAR and PVT1 (p = 0.0237) and enrichment was detected in the “development of carcinoma” (p = 0.0176). Two lncRNAs (HCG11, PART1) were positively correlated with 342 mRNAs, and their correlation estimates diminish after adjusting for either of the target miRNAs: hsa-miR-490-3p, hsa-miR-129-5p. This suggests a likely sponge function for HCG11 and PART1. Conclusions: These findings identify differential lncRNAs with oncogenic features that are associated with G-CIMP phenotypes. Further investigation with controlled experiments is needed to confirm the molecular relationships.

Original languageEnglish
Article number182
JournalJournal of Translational Medicine
Volume19
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Henry Ford Health System, Department of Neurosurgery and the Hermelin Brain Tumor Center Foundation. Additionally, ID, LMP and HN are supported by National Institutes of Health (R01CA222146) and HN and LMP are supported by Department of Defense (CA170278).

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • G-CIMP subtypes
  • Glioma
  • Long non-coding RNAs

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