circMRPL35 promotes gastric cancer progression through the miR-6809-3p/ZNF90 axis and affects the EMT process and TGF-β1/SMAD2/3 signaling.

[BACKGROUND] Circular RNAs (circRNAs) have been implicated in developing gastric cancer (GC). However, the role of circMRPL35 in GC remains unknown.

[METHODS] This study identified differentially expressed circMRPL35 using gene expression profiles GSE78092, GSE131414, and GSE100170. RNA R enzyme and RNA FISH assays were used to explore the origin, cyclization site, and cellular localization of circMRPL35. The functions of circMRPL35, miR-6809-3p, and ZNF90 in GC cells were evaluated through loss- and gain-of-function experiments. The epithelial-mesenchymal transition (EMT) process and the TGF-β1/SMAD signaling pathway were analyzed using Western blot and immunofluorescence assays. Subcutaneous tumor models in nude mice were utilized to evaluate the impact of circMRPL35 on GC cells. The interactions among circMRPL35, miR-6809-3p, and ZNF90 were confirmed through luciferase reporter and rescue assays.

[RESULTS] The study demonstrated that circMRPL35, present in the cytoplasm and nucleus of MGC-803 and HGC-27 cells, originates from the cyclization of exons 4 and 5 on chromosome 2. In GC tissues and cells, circMRPL35 and ZNF90 were upregulated, while miR-6809-3p was downregulated. circMRPL35 and ZNF90 enhanced cell mobility and invasion and suppressed apoptosis by modulating the EMT process and TGF-β1/SMAD2/3 signaling pathway; conversely, miR-6809-3p exhibited the opposite effects. Mechanistically, circMRPL35 sponges miR-6809-3p to regulate ZNF90, thereby enhancing the phenotype of GC cells.

[CONCLUSIONS] These results indicate that circMRPL35 acts as an oncogenic driver via the miR-6809-3p/ZNF90 axis, affecting the EMT process and the TGF-β1/SMAD2/3 signaling pathway to promote GC progression.