(1) These miRNAs are reported to be associated with the aggressiveness of lung cancers(2) Its over-expression down-regulates PTEN and TIMP3 to inhibit apoptosis and promotes cell migration(3) Interaction of extracellular HMGB1 with RAGE results in enhanced miR-221/222 cluster expression which sequentially inhibits tumor suppressor gene PTEN to facilitate tumor escape. The gene discussed is HMGB1; the disease is lung cancer.