Moreover, co-treatment with caspase inhibitor Z-VAD-FMK rescued from apoptosis, but not from p-H2AX increase induced by miR-22 overexpression (Supplementary Fig.5f), thus suggesting that miR-22 tumor suppressor activity on MM cells relies on activation of DDR, which in turn leads to caspase-dependent cell death due to accumulation of irreparable DNA damage. Here, H2AX is linked to neoplasm.