Figure 9.

Schematic for the regulatory network mediated by miR-M2-5p in promoting GaHV-2-induced tumorigenesis. The miR-M2-5p triggers the virally-induced T-cell lymphomagenesis by regulating both cell proliferation and apoptosis through multiple smart strategies, including regulating the RBM24-mediated p63 overexpression and the MYOD1-mediated IGF2 and Caspase-3 signaling pathways. In GaHV-2 infection, the expression levels of RBM24 and MYOD1 are both decreased by the viral miR-M2-5p targeting. As one of the consequences, the downregulation of RBM24 mediated by miR-M2-5p actually results in the p63 overexpression and promotes the cell proliferation. On the other hand, the decrease of MYOD1 induces the downregulations of gga-miR-1, gga-miR-206, and gga-miR-223 expressions. The downregulation of gga-miR-223 further inhibits the IGF2 expression and promotes the cell proliferation while the decreases of gga-miR-1 and gga-miR-206 expressions result in the upregulated Pax3 expression and activate two anti-apoptotic factors, Bcl-2, and Bcl-xL, which finally inhibit cell apoptosis. As a final result, all of the target-related signaling pathways involved above may contribute to increase the chances for potential cellular transformation in the virally-induced MD lymphomagenesis.