Recent research published in Gene investigates the relationship between mRNA and miRNA expression levels in different neuronal cell types and neuroblastoma. Using microarray analysis coupled with EGAN (Exploratory Gene Association Networks) software, Liu et al. studied the mRNA-miRNA expression relationships between three neuronal cell types: mature neurons and neural progenitor cells (derived from rat brain tissue) and neuroblastoma cells. The authors concluded that there are expression signatures of mRNA and miRNA transcripts characteristic of each of the different cell types. Most of the over-expressed mRNA transcripts found in mature neurons had low levels of expression in neuroblastoma cells and moderate expression in progenitor cells. The authors found this pattern to be true for transcripts over-expressed in neuroblastoma cells as compared to mature neurons, and that the pathways represented by the over-expressed transcripts in neuroblastoma were related to pathways specific to cancer. The results indicated that a portion of over-expressed mRNA transcripts in mature neuronal cells (or neuroblastoma cells) also had under-expressed miRNA species (within the same cell type) that are predicted to target the over-expressed mRNAs. Validation studies of specific mRNA-miRNA interactions were not reported in this article. The authors conclude their discussion by commenting on the possibility of mRNA-miRNA regulatory network signatures as a tool to identify novel tumor suppressor candidates.
These findings contribute to the growing list of evidence supporting the role of miRNA in cancer regulation as well as in normal tissue development. Liu et al. highlight the proposed interaction between tumor-associated factor Runx1 and miR-370. The expression of Runx1 and miR-370 is inversely proportional in neuroblastoma cells (high Runx1, low miR-370) and mature neurons (low Runx1, high miR-370) with moderate expression of both in neuroprogenitor cells. Their analysis did not confirm the direct regulation of Runx1 mRNA by miR-370, but the network analysis provided in this study may be able to lay the groundwork to isolate important miRNA candidates which are deregulated in neuronal cancers. Liu et al. shine some light onto the potential of studying miRNA regulation in normal tissue development as a mechanism of learning about normal, functioning pathways which become aberrantly regulated in cancer initiation and progression. Considering the relatedness of normal tissue development and cancer signaling, identifying novel miRNA networks in these two pathways (particularly normal tissue development) can contribute to our further understanding of cancer mechanisms.
Liu, Da-Zhi., et al.
Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells.
Gene. 495(2012): p. 120-127.