Long non-coding RNAs are involved in the activation of glycolysis in colorectal cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE139402 | GEO | 2021/02/23
REPOSITORIES: GEO
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Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPα/β transcription factors and CTCF, thereby governing intricate control of neuronal development.
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Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPM-NM-1/M-NM-2 transcription factors and CTCF, thereby governing intricate control of neuronal development. mRNA and long non-coding RNA expression profiling of maturing primary cortical neurons from E15 mouse embryos and neurons subjected to oxygen-glucose deprivation. Maturing neurons were harvested on Days 2, 4, 6 and 8. Neurons on Day 6 were subjected to oxygen-glucose deprivation for different time periods and 24 hours reperfusion before being harvested.
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Project description:Human genome encodes a multitude of different non-coding transcripts that have been traditionally separated based on their lengths into long or small non-coding RNAs. The vast majority of both long and short non-coding transcripts are not annotated and their functions, mechanisms of action and biological relevance remain unknown. However, based on the functional understanding of the known classes of long and small non-coding RNAs (sncRNAs) that have been shown to play crucial roles in multiple biological processes, it is generally assumed that many unannotated long and small transcripts participate in important cellular functions as well. Still, direct evidence of functionality is lacking for most non-coding transcripts, especially for sncRNAs that are often dismissed as stable degradation products of longer RNAs. Here, we have developed a high-throughput assay to test functionality of sncRNAs based on overexpressing them in human cells. Surprisingly, we found that a significant fraction (> 40%) unannotated sncRNAs appear to have biological relevance. Furthermore, contrary to the expectation, the potentially functional transcripts are not highly abundant and can be derived from protein-coding mRNAs. These results strongly suggest that the small non-coding transcriptome can harbor multiple functional transcripts that warrant future studies.
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