ZBTB7A, a miR-663a target gene, protects osteosarcoma from endoplasmic reticulum stress-induced apoptosis by suppressing LncRNA GAS5 expression

Many studies have uncovered the essential role of ZBTB7A in regulating tumourigenesis. However, its functional significance in cell responses to endoplasmic reticulum stress (ER stress) remains poorly understood. Here we report that ZBTB7A functions as an important prosurvival factor in osteosarcoma cells undergoing pharmacological ER stress-induced by tunicamycin (TM) or thapsigargin (TG). The downregulation of ZBTB7A expression by ER stress promoted cell apoptosis in vitro and in vivo. ZBTB7A expression levels were increased in osteosarcoma tissues and elevated ZBTB7A was associated with osteosarcoma metastasis. Further mechanistic studies revealed that miR-663a induced by ER stress directly bound to the 3'UTR of ZBTB7A and contributed to ER stress-induced ZBTB7A downregulation in osteosarcoma cells. Additionally, our data revealed that ZBTB7A bound to the promoter of LncRNA GAS5 and transcriptionally suppressed LncRNA GAS5 expression, leading to a decline in ER stress-induced cell apoptosis. Collectively, our findings reveal the prosurvival role of ZBTB7A in osteosarcoma adaptation to ER stress and suggest that the miR-663a-ZBTB7A-LncRNAGAS5 pathway is essential for the survival of human osteosarcoma cells under ER stress.