Figure 6. A proposed model showing the functional crosstalk between HOTAIR and YBX1.

Overexpression of HOTAIR leads to its interaction with both YBX1 and the kinases pAKT and pRSK, leading to enhanced YBX1 S102 phosphorylation. This in turn leads to YBX1 nuclear translocation, activating gene transcription, resulting in PI3K/ERK activation that drives further AKT and RSK phosphorylation in a positive feedback loop. This activated PI3K/Akt and ERK/RSK pathways further drive the phosphorylation and nuclear translocation of YBX1. HOTAIR is ultimately able to modulate cell proliferation in part via regulating the YBX1 target genes PCK2 and platelet derived growth factor receptor β.