Knockdown of Stromal Interaction Molecule 1 (STIM1) Suppresses Acute Myeloid Leukemia Cell Line Survival Through Inhibition of Reactive Oxygen Species Activities
Abstract Stromal interaction molecule 1 (STIM1) is a critical regulator of calcium homeostasis through store-operated calcium entry (SOCE) and recently considered a potential therapeutic target for cancer. However, the role of STIM1 in acute myeloid leukemia (AML) remains unclear. The present study investigates the role of STIM1 in AML cell line (THP-1) proliferation and survival and its effect on reactive oxygen species (ROS) activities. Dicer-substrate siRNA (dsiRNA) - mediated STIM1 knockdown inhibited the THP-1 cells proliferation and colony formation ability. Further observation on ROS profile showed a significant reduction in the ROS level, which was associated with a significant down-regulation of NOX2 and protein kinase C (PKC). Furthermore, STIM1 knockdown exhibited significant down-regulation of Akt, KRAS, and MAPK which are critical proliferative and survival pathway-related genes. This study unveiled the importance of STIM1 in the regulation of AML cells proliferation and survival which could be through maintaining ROS at level keeping the proliferative and survival pathways at an active state. These findings represent STIM1 as a potential therapeutic target for AML treatment.