Objectives
Circular RNAs (circRNAs) play pivotal roles in malignancies including gastric cancer (GC). We aimed to investigate the biological function and regulatory mechanism of circ_0006089 in GC.
Methods
Circ_0006089, microRNA (miR)‐143‐3p, and polypyrimidine tract‐binding protein 3 (PTBP3) expressions were measured via quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) in GC cell lines. Cell proliferative capacity was determined by colony formation and CCK‐8 assays. Flow cytometry was employed for measuring cell apoptosis. Cell invasion and migration were measured via transwell and wound‐healing assays. Western blot analysis was utilized for detecting protein expressions of E‐cadherin, N‐cadherin, vimentin, PTBP3, PI3K, p‐PI3K, AKT, and p‐AKT. Dual‐reporter luciferase analysis was conducted to confirm the association between miR‐143‐3p and circ_0006089 or PTBP3. The role of circ_0006089 in vivo was detected via establishing a mice xenograft model.
Results
Circ_0006089 expression was increased in GC. Circ_0006089 downregulation suppressed the proliferation and metastasis and induced apoptosis of GC cells, which was counteracted by miR‐143‐3p inhibition or PTBP3 overexpression. In addition, circ_0006089 overexpression could promote GC progression. MiR‐143‐3p specially bound to circ_0006089 and PTBP3 was targeted by miR‐143‐3p. Moreover, circ_0006089 could regulate PTBP3 expression and the PI3K/AKT pathway by sponging miR‐143‐3p. Circ_0006089 knockdown also suppressed tumor growth.
Conclusion
Circ_0006089 regulated miR‐143‐3p/PTBP3/PI3K/AKT pathway to facilitate GC progression.