CREB1-induced lncRNA LOC100270746 promotes gastric cancer progression via stabilizing DDX5 and activating the mTOR pathway

Gastric cancer is one of the most common malignancies, with limited treatment options and a poor prognosis. cAMP responsive element binding protein 1 (CREB1), as a transcription factor, is a critical regulator of cancer progression. However, whether CREB1-mediated lncRNA transcription is involved in gastric cancer progression remains to be investigated. In this study, genome-wide binding of CREB1 in gastric cancer was determined by chromatin immunoprecipitation sequencing (ChIP-seq), and the expression of CREB1 and lncRNA LOC100270746 was determined. In vitro and in vivo functional assays were used to explore the roles of LOC100270746. The regulatory axis of the CREB1/LOC100270746/DDX5 axis was investigated by ChIP, luciferase, RNA pull-down, RNA immunoprecipitation, and Western blot. Up-regulated CREB1 expression in gastric cancer was correlated with poorer prognosis, and it contributed to the proliferation, migration, and invasion of gastric cancer. CREB1 bound to the promoter region of LOC100270746 and up-regulated its expression, which increased the proliferation, migration, and invasion of gastric cancer. Mechanistically, LOC100270746 could directly bind to DDX5 and enhance its stability. LOC100270746 promoted gastric cancer progression and regulated the mTOR pathway through DDX5. The oncogenic functions of both LOC100270746 and DDX5 were highly dependent on mTOR pathway activation. In conclusion, CREB1-induced lncRNA LOC100270746 promotes gastric cancer progression by stabilizing DDX5 and activating the mTOR pathway. LOC100270746, a critical mediator of CREB1 signaling, may serve as a target for gastric cancer therapies.