circSLC4A7 accelerates stemness and progression of gastric cancer by interacting with HSP90 to activate NOTCH1 signaling pathway

Gastric cancer stem cells (GCSCs) play critical roles in gastric cancer (GC) initiation and development. Circular RNAs (circRNAs) participate in diverse cancer biological processes and function as tumor suppressors or oncogenes. This study aims to discover the expression profile and functional roles of circRNAs in GCSCs. A spheroid formation assay was conducted to enrich GCSCs. Genome-wide sequencing of circRNAs showed that a novel circRNA, circSLC4A7, was one of the most upregulated circRNAs in GCSCs. CircSLC4A7 was localized to the nucleus, and its level was elevated in GC cells and tissues. Furthermore, circSLC4A7 increased CSC-like properties and drove cell proliferation, migration, and invasion, which were determined by gain- and loss-of-function experiments. Specific circRNA pull-down assays followed by mass spectrometry analysis, RNA immunoprecipitation, and dual RNA-fluorescence in situ hybridization and immunofluorescence assay were conducted and HSP90 was detected to interact with circSLC4A7 and mediate the oncogenic function of circSLC4A7 by activating the Notch1 signaling pathway in GC. This study highlights a novel oncogenic function of circSLC4A7 mediated by its binding with HSP90 and thus activating the Notch1 signaling pathway.