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Published on: March 30, 2019
CircVDAC3 sequesters microRNA-592 and elevates EIF4E3 expression to inhibit the progression of gastric cancer
Tian-Ning Yang1, Ruo-Wen Xiao2, Fei Su1
1The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, PR China; Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, PR China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Circular RNA VDAC3 (circVDAC3) is downregulated in gastric cancer (GC) and inhibits tumor growth and metastasis. It functions via the circVDAC3/miR-592/EIF4E3 pathway, offering potential therapeutic targets for GC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in gastric cancer (GC) development.
- Specific functional circRNAs and their mechanisms in GC require further investigation.
Purpose of the Study:
- To identify and elucidate the function and mechanism of a novel circRNA in gastric cancer.
Main Methods:
- Differential expression analysis of circRNAs using microarray data.
- Validation of circVDAC3 expression and structure via qRT-PCR and other assays.
- Functional studies including cell-based assays and animal models.
- Mechanistic investigations using bioinformatics, FISH, and dual luciferase assays.
Main Results:
- circVDAC3 expression is downregulated in GC tissues.
- circVDAC3 suppresses GC cell proliferation and metastasis.
- circVDAC3 acts as a competing endogenous RNA (ceRNA) for miR-592, thereby regulating EIF4E3 expression.
- EIF4E3 is downregulated in GC, and its repression by miR-592 is linked to circVDAC3's anticancer effects.
Conclusions:
- circVDAC3 inhibits GC growth and metastasis through the circVDAC3/miR-592/EIF4E3 axis.
- This pathway provides novel insights into GC tumorigenesis.
- circVDAC3 represents a potential therapeutic target for gastric cancer.
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