Abstract: Background and purpose: Gastric cancer is the most common malignant tumor of digestive tract. Circ_0007142 has been proved to be a carcinogenic factor of colorectal cancer and can promote the progression of colorectal cancer. This study aimed to explore the effects of circ_0007142 on epithelial-mesenchymal transition (EMT) and invasion of gastric cancer cells via absorbing miR-647 and then regulating CCR8 gene. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expressions of circ_0007142, miR-647 and CCR8 in gastric cancer tissues and cells. Fluorescence in situ hybridization (FISH) experiment was adopted to determine the subcellular localization of circ_0007142. Dual luciferase reporter experiment and RNA immunoprecipitation (RIP) assay were used to confirm the targeting relationship of circ_0007142 and miR-647 as well as miR-647 and CCR8. Transwell assay, clone formation assay and Western blot were used to test the cell invasion ability, clonality and EMT respectively. Tumor xenograft in BALB/c nude mice was performed to detect tumorigenicity of circ_0007142 in vivo. Results: Overexpressions of circ_0007142 and CCR8 and downregulation of miR-647 were detected in gastric cancer tissues and cells. Circ_0007142 acted as a molecular sponge to inhibit the expression of miR-647, at the same time, miR-647 inhibited the expression of CCR8 by binding with the 3'-UTR of CCR8 mRNA. Knockdown of circ_0007142 or overexpression of miR-647 inhibited the invasion, colony formation and EMT of gastric cancer cells. However, the effects of circ_0007142 inhibition or miR-647 overexpression on gastric cancer cells were partially reversed by miR-647 inhibitor or CCR8 overexpression (all P<0.05). Moreover, knockdown of circ_0007142 in gastric cancer cells inhibited the tumor growth in vivo. Conclusion: Circ_0007142 upregulates the expression of CCR8 via sponging miR-647, which subsequently accelerates the EMT and invasion of gastric cancer cells and promotes the progression of gastric cancer.

Key words: Circ_0007142, miR-647, CCR8, Gastric cancer, Epithelial-mesenchymal transition, Invasion