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MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer

Godlewski, Jakub, Lenart, Jacek, Salinska, Elzbieta·2019·Non-Coding RNA
DOI 10.3390/ncrna5010020PMC PMC6468660
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Abstract

The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and cellular factors in glial cells, and less frequently in neurons, drive oncogenic transformation. In both situations, microenvironmental niches influence the progression of diseases and therapeutic responses. Dynamic changes that occur in cellular transcriptomes during the progression of developmental lineages and pathogenesis are controlled through a variety of regulatory networks. These include epigenetic modifications, signaling pathways, and transcriptional and post-transcriptional mechanisms. One prominent component of the latter is small non-coding RNAs, including microRNAs, that control the vast majority of these networks including genes regulating neural stemness, differentiation, apoptosis, projection fates, migration and many others. These cellular processes are also profoundly dependent on the microenvironment, stemness niche, hypoxic microenvironment, and interactions with associated cells including endothelial and immune cells. Significantly, the brain of all other mammalian organs expresses the highest number of microRNAs, with an additional gain in expression in the early stage of neurodegeneration and loss in expression in oncogenesis. However, a mechanistic explanation of the concept of an apparent inverse correlation between the odds of cancer and neurodegenerative diseases is only weakly developed. In this review, we thus will discuss widespread de-regulation of microRNAome observed in these two major groups of brain pathologies. The deciphering of these intricacies is of importance, as therapeutic restoration of pre-pathological microRNA landscape in neurodegeneration must not lead to oncogenesis and vice versa. We thus focus on microRNAs engaged in cellular processes that are inversely regulated in these diseases. We also aim to define the difference in microRNA networks between pro-survival and pro-apoptotic signaling in the brain.

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Figure 1 Gene Venn showing microRNA under investigation in selected pathologies of the brain (based on Table 2) (Brain Cancer (BC), Neurodegenerative Disorders (ND) Ischemia (IH)). MiR-21, let-7, miR-210 and miR-128 are common microRNAs.
Figure 1 Gene Venn showing microRNA under investigation in selected pathologies of the brain (based on Table 2) (Brain Cancer (BC), Neurodegenerative Disorders (ND) Ischemia (IH)). MiR-21, let-7, miR-210 and miR-128 are common microRNAs.CC BY · PubMed Central

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Metadata

Authors
Godlewski, J., Lenart, J., & Salinska, E.
Affiliations
  • Affiliation Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Affiliation Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland
ORCID
Salinska, Elzbieta
Venue
Non-Coding RNA
Publisher
MDPI AG
Published
2019-02-23
Volume
5
Issue
1
Pages
20
ISSN
2311-553X
DOI
10.3390/ncrna5010020
PMC
PMC6468660
Cited by
52
References
15
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institutes of Health (NCI 1R01 CA176203-01A1)
  • Narodowe Centrum Nauki (NCN 2014/15/B/NZ4/04487)

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