Abstract
BackgroundGastric cancer (GC) is one of the most common cancers in the digestive system. Circular RNAs (circRNAs) have been found to function as important regulators in the pathogenesis of GC. This study focused on the biological role and molecular mechanism of circ_0000620 in GC progression.MethodsThe expression levels of circ_0000620, microRNA-671-5p (miR-671-5p) and Matrix MetalloProteinase 2 (MMP2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) assay or western blot. The stability of circ_0000620 was confirmed by Ribonuclease R (RNase R) assay. The protein levels were determined by western blot assay. Cell viability, colony formation, cell migratory ability, cell invasive ability and tube formation capacity were respectively examined by CCK-8 assay, colony formation assay, wound healing assay, transwell invasion assay and tube formation assay. The interaction between miR-671-5p and circ_0000620 or MMP2 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The role of circ_0000620 in GC undefined was explored by xenograft tumor assay.ResultsCirc_0000620 was conspicuously upregulated in GC tissues and cells. Circ_0000620 knockdown reduced cell viability, colony formation, migration, invasion and tube formation capacity of GC cells in vitro. Furthermore, MMP2 was upregulated in GC and MMP2 overexpression reversed the anti-tumor response of circ_0000620 knockdown in GC progression. Moreover, circ_0000620 directly interacted with miR-671-5p and circ_0000620 downregulation regulated malignant behaviors of GC cells by upregulating miR-671-5p. In addition, silencing of circ_0000620 inhibited tumor growth in vivo.ConclusionsCirc_0000620 knockdown inhibited the malignant development of GC partly through modulating the miR-671-5p/MMP2 axis.
Highlights
Gastric cancer (GC) is one of the most common cancers in the digestive system
The survival analysis revealed that survival rate was decreased in GC patients with high circ_0000620 expression compared to those patients with low circ_0000620 expression, suggesting that circ_0000620 could predict poor prognosis for GC patients (Fig. 1B)
Ribonuclease R (RNase R) assay presented that RNase R reduced the expression of linear alpha and gamma adaptin binding protein (AAGAB) mRNA but did not affect the expression of circ_0000620 compared to Mock group (Fig. 1E, F), implying that circ_0000620 was highly stable in GC cells
Summary
Circular RNAs (circRNAs) have been found to function as important regulators in the pathogenesis of GC. This study focused on the biological role and molecular mechanism of circ_0000620 in GC progression. Gastric cancer (GC) is one of the most common malignancies and accounts for cancer-induced deaths worldwide, especially in China [1,2,3]. Ren et al Journal of Biological Research-Thessaloniki (2021) 28:23 it is necessary to investigate the molecular mechanism related with tumor metastasis and angiogenesis in GC. CircRNAs exhibit many molecular functions, such as microRNA (miRNA) sponges or protein scaffolding in the progression of human malignancies [14, 15]. The biological function and molecular mechanism of circ_0000620 in GC remain to be explored
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