IL11RA signaling and EZH2 activity in osteosarcoma

Lung metastasis is the principal cause of death by osteosarcoma (OS), and has been shown by in vivo modeling to depend on interleukin-11 receptor alpha (IL11RA). To investigate IL11RA signaling in OS, we determined the effects of IL11RA knockdown on gene expression in the OS cell line KRIB. Increased expression of genes repressed by the methyltransferase EZH2 was observed after IL11RA knockdown. Subsequent studies confirmed that IL11RA signaling promotes EZH2 activity and lung metastasis in OS. Gene expression in KRIB cells with 4 different shRNA sequences targeting EZH2 was compared to that in control cells. The most compelling results were for the 3 shRNA sequences with the greatest knockdown of IL11RA: C1, H8, and H2.