Similar with the study showing that NOX4-dependent ROS generation contributes to hypoxia-induced IL-6 production in renal cell carcinoma cells [18], in the present study, we found that NOX4 could enhance IL-6 expression and stimulate its downstream JAK/STAT3 signaling in NSCLC cells through stimulation of PI3K/Akt pathway. The gene discussed is AKT1; the disease is hereditary clear cell renal cell carcinoma.