Long non-coding RNA profiling of pediatric Medulloblastoma

Abstract

Background Medulloblastoma (MB) is one of the most common malignant cancers in children. MB is primarily classified into four subgroups based on molecular and clinical characteristics as (1) WNT (2) Sonic-hedgehog (SHH) (3) Group 3 (4) Group 4. Molecular characteristics used for MB classification are based on genomic and mRNAs profiles. MB subgroups share genomic and mRNA profiles and require multiple molecular markers for differentiation from each other. Long non-coding RNAs (lncRNAs) are more than 200 nucleotide long RNAs and primarily involve in gene regulation at epigenetic and post-transcriptional levels. LncRNAs have been recognized as diagnostic and prognostic markers in several cancers. However, the lncRNA expression profile of MB is unknown. Methods We used the publicly available gene expression datasets for the profiling of lncRNA expression across MB subgroups. Functional analysis of differentially expressed lncRNAs was accomplished by Ingenuity pathway analysis (IPA). Results In the current study, we have identified and validated the lncRNA expression profile across pediatric MB subgroups and associated molecular pathways. We have also identified the prognostic significance of lncRNAs and unique lncRNAs associated with each MB subgroup. Conclusions Identified lncRNAs can be used as single biomarkers for molecular identification of MB subgroups that warrant further investigation and functional validation.

Identification of Potential lncRNAs and miRNAs as Diagnostic Biomarkers for Papillary Thyroid Carcinoma Based on Machine Learning

“…Our result indicated that interaction pairs of MIR181A2HG-FOXP2-hsa-miR-146b-3p may be associated with PTC. e expression of BLACAT1 is increased in some cancers, such as medulloblastoma, colon adenocarcinoma, pancreatic adenocarcinoma, gastric cancer, and TC [30][31][32][33][34][35]. Moreover, BLACAT1 has a prognostic value for patients with PTC [36].…”

“…LBX2-AS1 is upregulated in PTC and TC [37]. MIR100HG is downregulated in pediatric medulloblastoma [31]. In gastric cancer, downregulation of MIR100HG inhibits cell proliferation and migration [40].…”

Roles of lncRNAs in childhood cancer: Current landscape and future perspectives

“…There is a pressing need to identify the underlying molecular pathways in these subgroups in order to promote precision medicine-based therapies, improve quality of life, and expand our overall understanding of MB (122). By searching Gene Expression Omnibus (GEO) database for MB related microarray datasets, Kesherwani and colleagues determined the prognostic relevance of lncRNAs and the distinct lncRNAs associated with each MB subgroup (123). Through a joint analysis of the RNA-seq data from the European Genome-Phenome Archive (EGA) and two studies of MB from GEO, the research team from Johns Hopkins University identified 17 putative candidate lncRNAs that could be used as progression or as diagnostic and prognostic biomarkers (124).…”

Subgroup-Specific Diagnostic, Prognostic, and Predictive Markers Influencing Pediatric Medulloblastoma Treatment

“…One of these studies validated the top 10 oncogenic or tumor suppressive lncRNAs in each MB subgroup and explored their associated molecular pathways. Among these identified lncRNAs, high expression of HAND2-AS1 in WNT-MB, low expression of MEG3 in SHH-MB, high expression of DLEU2 and DSCR8 in group 3 MB, and high expression of DLEU2 and low expression of XIST in group 4 were associated with poor prognosis [ 183 ]. In this manner, lncRNAs may be exploited as prognostic biomarkers for molecular identification of MB subgroups.…”