In this report, we found that the K7 of Rab22a-NeoF1, acetylated by p300/CBP while de-acetylated by both HDAC6 and SIRT1, plays a key role in its binding to SmgGDS607, and consequently affects its activation of RhoA and promotion of cell migration, invasion and lung metastasis in osteosarcoma. The gene discussed is RHOA; the disease is osteosarcoma.