MicroRNA 675 cooperates PKM2 to aggravate progression of human liver cancer stem cells induced from embryonic stem cells.

Both miR675 and pyruvate kinase M2 (PKM2) contribute to malignant progression of tumor, but its functions in liver cancer stem cells remain unclear. Herein, our findings indicate that miR675 plus PKM2 strongly promotes the growth of liver cancer stem cells. Mechanistically, miR675 plus PKM2 enhances the transcriptional activity of SUV39h2. On the other hand, the excessive SUV39h2 binds to more substrate histone H3, triggering an increase of tri-methylation of histone H3 on the ninth lysine. Furthermore, the tri-methylation of histone 3 on the ninth lysine (H3K9me3)-heterochromatin protein 1 alpha (HP1α) complex is increased when the complex occupancy ability on the C-myc promoter region is raised, recruiting CREB, P300, and RNApolII to the special position that results in C-myc high abundance. Therefore, miR675 plus PKM2 triggered the upregulation of C-myc by increasing the interaction between H3K9me3 and HP1α. Understanding the signaling pathways that miR675 plus PKM2 epigenetically possesses during the malignant transformation of liver cancer stem cells will contribute to more effective liver cancer therapies.