CircVDAC3 sequesters microRNA-592 and elevates EIF4E3 expression to inhibit the progression of gastric cancer

• Published in: Translational oncology 2024-07, Vol.45, p.101972-101972, Article 101972
• Main Authors: Yang, Tian-Ning, Xiao, Ruo-Wen, Su, Fei, Dai, Huan-Yu, Zhao, Da, Guo, Chen-Hao, Zhu, Kai-Li, Jiang, Nan, Guan, Quan-Lin, Hou, Xiao-Ming
• Format: Article
• Language: English
• Subjects: CeRNA; CircVDAC3; EIF4E3; Gastric cancer; MiR-592
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2024.101972

•CircVDAC3 is downregulated in gastric cancer.•Overexpression of circVDAC3 inhibits the proliferation and metastasis of gastric cancer cells in vitro and in vivo.•CircVDAC3 is localized in the cytoplasm and act as a miR-592 sponge.•CircVDAC3 competitively binds to miR-592 to up-regulate EIF4E3 expression, thereby inhibit the growth and metastasis of gastric cancer cells. Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies. [Display omitted]