Figure 10

Model of the proposed regulatory network of chicken cell proliferation. The miR-17-92 cluster, MAP3K2, E2F1 and c-Myc form a complex regulatory feedback network to regulate chicken cell proliferation. The miR-17-92 cluster promotes chicken cell proliferation via upregulation of c-Myc by targeting MAP3K2, which inhibits c-Myc expression through the MAPK signaling pathway. In addition to MAP3K2, the miR-17-92 cluster can also promote cell proliferation via targeting other target genes such as PTEN and TGFBR2. The c-Myc and E2F1 can activate the transcription of each other, and both of them directly promote the miR-17-92 cluster expression. However, the miR-17-92 cluster postranscriptionally suppresses E2F1 expression through its two members (miR-17-5p and miR-20a). thus counterbalancing the positive feedback loop of E2F1 and c-Myc. Darker lines denote evidence provided in the present study, and the dashed lines denote evidence based on the literature [17, 58].