Circ_0001451 inhibits gastric cancer metastasis via miR-197-3p /MT3 axis

Abstract Background CircRNAs, new non-coding RNA as miRNA sponge, play crucial roles in tumor initiation and development. The present study aimed to identify hsa_circ_0001451 and its related molecules for the progression of gastric cancer. Methods The expression of hsa_circ_0001451 was determined in 66 cases of paired gastric cancer and their adjacent normal gastric tissues by qRT-PCR. The cellular localization of hsa_circ_0001451 was detected with FISH analysis. The biofunction alterations of hsa_circ_0001451 were assessed by its overexpression or knockdown in gastric cancer cell lines. MTS and cloning assay were used to detect cell proliferation. Flow cytometry was used to detect cell cycle. The wound healing and transwell assays were used for cell migration and invasion. Western Blotting was used to detect the expression of a set of genes related proliferation and migration. RNA immunoprecipitation (RIP), biotinylated RNA pull-down and dual luciferase reporter tests were used to detect the interactions of hsa_circ_0001451with mir-197-3p / MT3. The in vivo proliferation and migration ability of hsa_circ_0001451infected cells were determined in zebrafish system. Results Hsa_circ_0001451 was decreased in 66 cases of gastric cancer tissues and cell lines, and significantly related to tumor invasion. The in vitro and in vivo studies indicated that over-expression of hsa_circ_0001451 inhibited the gastric cancer cell proliferation, invasion and migration via suppression of PCNA, CCND1 and BCL-2, and decreased in the S-phase. The results of pull-down, RNA immunoprecipitation and dual-luciferase reporter tests revealed that hsa_circ_0001451 could sponge miR-197-3p, targeting MT3 and affecting the malignancy of gastric cancer cells via regulating EMT related E-cadherin, N-cadherin, MMP7 and VIMENTIN. Conclusion This study revealed that hsa-circ-0001451 inhibited proliferation, invasion and metastasis and modulated EMT of gastric cancer cells via sponging of miR-197-3p and regulatng the downstream MT3. The circ_0001451 / miR-197-3p / MT3 axis are likely to be the biomarkers for prognosis and targets for drug of gastric cancer.