Figure 7.

Network model summarizing the role of miR-17-5p in promoting cellular proliferation. (a) An integrated network model of results presented in this study. Each node present is either a possible (light green) or a confirmed/literature supported target of miR-17-5p (dark green). The shape of each node reflects whether the gene product encodes a pro-proliferative signal (square) or anti-proliferative signal (circle). The edges represent published interactions between nodes and are classified as either activation (arrowheads) or inhibition (perpendicular ends). All edges are supported by at least one reference from the literature. Finally, nodes whose mRNA levels have been examined by qRT-PCR appear in the grey boxes, and those with similar expression profiles are grouped together. This analysis shows that while miR-17-5p targets both pro- and anti-proliferative targets, pro-proliferative targets are specifically up-regulated in the HEK293T-17-5p network. (b) A proposed model depicting the ability of miR-17-5p to act as both a tumor suppressor and an oncogene, depending on the cellular context, and using the same color and shape schema as above. In a situation where pro-proliferative genes dominate (left), suppression of anti-proliferative targets is reinforced by removal of self-regulatory signals and increased suppression by pro-proliferative regulators. These signals combine and lead to a net proliferative (oncogenic) outcome. In situations where anti-proliferative genes dominate (right), suppression of pro-proliferative signals is reinforced, leading to a net anti-proliferative signal. In this case, removal of miR-17-5p results in a pro-proliferative signal - a classic tumor suppressor outcome.