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Circ-DB participates in the progression of gastric cancer by competitively binding microRNA-34a to regulate the
Objective:
To figure out the possible role and mechanism of circ-DB in the pathogenesis of gastric cancer (GCa).
Patients And Methods:
32 cases of postoperative GCa tissue samples and adjacent ones were collected and divided into groups of ≥ 5 cm and < 5 cm according to tumor diameter. Circ-DB, microRNA-34a, and MET expressions were detected by real time-quantitative PCR (RT-qPCR) in GCa tissues and adjacent tissues. To determine the main mode of action of circ-DB, the subcellular localization of circ-DB was examined by dividing the cells into the nucleus and cytoplasmic fractions. The binding of microRNA-34a to circ-DB was demonstrated by a Dual-Luciferase reporter gene assay. The expression of circ-DB in HGC-27 and AGS cells was overexpressed and knocked down to evaluate the migration function of the cells by transwell. The protein expression of MET, as well as the target gene of microRNA-34a, was detected by Western blot.
Results:
The expression of circ-DB and MET in GCa tissues was significantly higher than that in the corresponding adjacent tissues. Circ-DB was positively correlated with MET expression, while microRNA-34a expression was negatively correlated with circ-DB and MET expression. Circ-DB was mainly located in the cytoplasm, and the Dual-Luciferase reporter gene demonstrated that microRNA-34a can bind to circ-DB. The down-regulation of circ-DB expression inhibited the migration of HGC-27 and AGS cells. In vitro cell experiments showed that low expression of circ-DB inhibited cell migration, which could be recovered by the co-transfection with microRNA-34a inhibitor.
Conclusions:
Circ-DB may regulate MET level through microRNA-34a and affect the proliferative ability and migration of GCa cells.
Insights
Circular RNA DB (circ-DB) promotes gastric cancer (GCa) cell migration by regulating MET expression via microRNA-34a. Inhibiting circ-DB reduces GCa cell proliferation and migration, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GCa) is a significant global health concern with complex pathogenesis.
- Circular RNAs (circRNAs) are emerging as key players in various cancers, including GCa.
Purpose of the Study:
- To elucidate the role and underlying mechanism of circ-DB in gastric cancer development.
- To investigate the interaction between circ-DB, microRNA-34a, and MET in GCa cells.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blot were used to assess gene and protein expression in GCa tissues and cell lines.
- Subcellular localization, Dual-Luciferase reporter assays, and transwell migration assays were performed to determine circ-DB function and interactions.
- circ-DB and microRNA-34a expression were manipulated (overexpression/knockdown) to evaluate their effects on GCa cell behavior.
Main Results:
- circ-DB and MET expression were significantly upregulated in GCa tissues compared to adjacent tissues.
- circ-DB positively correlated with MET and negatively correlated with microRNA-34a expression.
- circ-DB, primarily in the cytoplasm, binds to microRNA-34a, inhibiting GCa cell migration; this effect was reversed by microRNA-34a inhibition.
Conclusions:
- circ-DB promotes GCa cell proliferation and migration.
- circ-DB may act as a molecular sponge for microRNA-34a, thereby regulating MET expression and influencing GCa progression.
- circ-DB represents a potential therapeutic target for gastric cancer treatment.