Fig. 3

Molecular mechanisms of HOTAIR activity to promote cell proliferation. It is proposed that IRF-1 could negatively regulate HOTAIR expression. Activity of HOTAIR could induce CDK1 and CDK2 activity, leading to phosphorylation of EZH2 in the PRC2. Interaction of HOTAIR and PRC2 causes methylation of STAT3. This subsequently contributes to STAT3 phosphorylation, as activated form of protein, recruiting Cyclin D1. Additionally, could positively regulate HOTAIR activity, by affecting the corresponded gene promoter. Collaboration of Cyclin D1 with CDK4 and CDK6 coordinates in post-translational phosphorylation of some proteins and activity of some necessary transcription factors required for transition of G1 to S cell cycle. Alternatively, activity of HOTAIR could down-regulate p27. Defect of this protein could negatively promote activity of Cyclin D-CDK4 and Cyclin E-CDK2. This consequently promotes cell proliferation by contributing to G1 to S phase transition