Induction of miR-224 by Reactive Oxygen Species Regulates RASSF6 and Thus Modulates Malignant Behaviors and Chemosensitivity in Esophageal Squamous Cell Carcinoma

Esophageal cancer is one of the most common malignant tumors of the digestive tract, and miR-224 can promote the hypoxia tolerance of esophageal cancer cells. The expression of miR-224 and HIF-1α in esophageal cancer cells under hypoxic induction and their relationship with ROS was studied using RT-qPCR and Western Blot assays; cell viability and apoptosis under hypoxia, as well as the effects of miR-224 on cell proliferation and drug resistance, were investigated using CCK8, Annexin V-FITC/PI, H2DCFDA staining and Western Blot assays. Under hypoxic induction, miR-224 and HIF-1α expressions were upregulated, with the upregulation of miR-224 being related to ROS accumulation, while HIF-1α upregulation was not affected by ROS. Furthermore, the upregulation of miR-224 facilitated the survival of esophageal cancer cells under hypoxic conditions and reduced their chemosensitivity to CDDP. This effect was also validated in vitro, as miR-224 overexpression promoted the malignant behaviors in ESCC cells. Under hypoxic induction, ROS accumulation can lead to the upregulation of miR-224. MiR-224 facilitates the survival of esophageal cancer cells under hypoxic conditions and induces chemotherapeutic drug resistance.